成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	曾柏鈞 Tseng, Po-Chun
論文名稱：	探討胃癌細胞對丙型干擾素的感受性及其致癌性的調控 Investigating IFN-gamma Susceptibility and Oncogenic Regulation in Gastric Cancer Cells
指導教授：	沈延盛 Shan, Yan-Shen
學位類別：	博士 Doctor
系所名稱：	醫學院 - 臨床醫學研究所 Institute of Clinical Medicine
論文出版年：	2016
畢業學年度：	104
語文別：	英文
論文頁數：	112
中文關鍵詞：	丙型干擾素、轉錄激活因子1 、半乳糖苷結合凝集素-3 、肝醣合成酶激酶-3β 、整合素連接激酶、細胞生長、胃癌
外文關鍵詞：	IFN-γ, STAT1, Galectin-3, GSK-3β, ILK, Cell growth, Gastric cancer
相關次數：	點閱：188 下載：2
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

AKT調控的肝醣合成酶激酶-3β活化可以透過抑制Src homology-2 domain-containing phosphatase (SHP) 2進而促進丙型干擾素的訊號傳遞。而在人類胃癌AGS細胞，發生突變的磷酸肌醇3激酶 (PI3K) 以及磷酸酶與張力蛋白同源物 (PTEN) 則會造成AKT活化和肝醣合成酶激酶-3β的抑制進而活化SHP2而造成丙型干擾素的低感受性。在這裡，我們想要研究是否有些分子會促進AKT活化，抑制肝醣合成酶激酶-3β而使的活化SHP2，並造成丙型干擾素的抗性。首先，探討於胃癌細胞中，位於AKT上游的半乳糖苷結合凝集素-3 (galectin-3)所扮演的潛在角色。發現透過增加或是減少半乳糖苷結合凝集素-3的表現會改變丙型干擾素的訊號傳遞。藉由順鉑 (cisplatin) 所誘導半乳糖苷結合凝集素-3的表現量增加，存活細胞會產生丙型干擾素低感受性。進一步發現，半乳糖苷結合凝集素-3造成丙型干擾素抗性無關於胞外β-半乳糖苷酶 (β-galactoside) 的結合活性。此外半乳糖苷結合凝集素-3的表現量不受磷酸肌醇3激酶活化或是磷酸酶與張力蛋白同源物缺失所調控。而半乳糖苷結合凝集素-3的增加可以藉由促進PDK1媒介AKT在蘇氨酸位點的磷酸化進而使得肝醣合成酶激酶-3β抑制及SHP2活化。過度表現AKT、去活化型的肝醣合成酶激酶-3β、SHP2以及活化型的SHP2D61A將造成原先丙型干擾素敏感性的MKN45細胞發生低感受性。另外於AGS細胞減少半乳糖苷結合凝集素-3的表現量將可促進丙型干擾素誘導細胞生長抑制以及細胞凋亡。在第一部分，這些結果都證實增加半乳糖苷結合凝集素-3促進AKT/肝醣合成酶激酶-3β/SHP2的訊號傳遞，造成細胞對丙型干擾素的低感受性。整合素連接激酶是一個絲氨酸/蘇氨酸的激酶，特別是透過促進AKT活化以調節細胞黏附、遷移以及增生等功能。然而，胃癌細胞中異常的整合素連接激酶表現卻不會影響AKT/肝醣合成酶激酶-3β以及丙型干擾素所活化IRF1的訊號傳遞，指出了整合素連接激酶無法導致丙型干擾素抗性的發生。但是在AGS細胞當中，整合素連接激酶調控的角色並不清楚。而過去研究中，整合素連接激酶的表現量增加和腫瘤的分期及轉移有關。然而對於整合素連接激酶過度表現的調控以及整合素連接激酶如何調控胃癌發生的機制並無充分論述。我們發現整合素連接激酶的訊號傳遞透過ERK1/2/NF-κB以誘導細胞增生、遷移以及生存功能的角色。利用基因剃除以及藥物學的方法抑制整合素連接激酶可以降低NF-κB調控細胞增生。進一步發現整合素連接激酶可以透過IQGAP1以及Ras形成複合物遂而刺激Ras的活性致使c-Raf/MEK1/2/RSK/IκBα/NF-κB活化。研究結果證實具有酵素特性的整合素連接酶區段可以藉由ERK1/2/NF-κB訊號而促進細胞增生。透過磷酸肌醇3激酶的活化以及磷酸酶與張力蛋白同源物的缺失可以避免蛋白酶體 (proteasome) 所誘導的蛋白降解而保護整合素連接激酶維持ERK1/2的活性。HSP-90相關的E3泛素連接酶CHIP也可藉由整合素連接激酶的泛素化 (ubiquitination) 而控制磷酸肌醇3激酶以及HSP90所調控整合素連接激酶的穩定性以及訊息傳遞。除了細胞增生之外，此一傳遞路徑亦促進細胞遷移以及增加對於抗腫瘤藥物5-fluorouracil及順鉑的抗藥性。此外，表皮生長因子 (EGF)/表皮生長因子受器 (EGFR) 的訊息也可以驗證整合素連接激酶和IQGAP1對於ERK所調控的角色。這些結果都將證實整合素連接激酶的增加促進IQGAP1以及Ras之間相互作用，並藉由非傳統路徑促進ERK1/2/NF-κB活化進而促進細胞生長。綜合以上，我們在胃癌細胞證實丙型干擾素的感受性及其致癌性的調控。

AKT regulates activated glycogen synthase kinase (GSK)-3β to facilitate IFN-γ signaling through the inhibition of Src homology-2 domain-containing phosphatase (SHP) 2. Mutated phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) cause AKT activation and GSK-3β inactivation to induce SHP2-activated cellular hyporesponsiveness to IFN-γ in human gastric cancer AGS cells. Here, we want to discover whether some molecules for promoting AKT activation, GSK-3β inactivation, and SHP2 activation to cause IFN-γ resistance. First, the potential role of galectin-3 acts upstream of AKT will be investigated. Increasing or decreasing galectin-3 could change IFN-γ signaling. Following cisplatin-induced galectin-3 up-regulation, surviving cells showed cellular hyporesponsiveness to IFN-γ. Galectin-3 induced IFN-γ resistance independent of its extracellular β-galactoside-binding activity. Galectin-3 expression was not regulated by PI3K activation or a decrease in PTEN. Increased galectin-3 might cause GSK-3β inactivation and SHP2 activation by promoting PDK1-induced AKT phosphorylation at a threonine residue. Overexpression of AKT, inactive GSK-3βR96A, SHP2, or active SHP2D61A caused cellular hyporesponsiveness to IFN-γ in IFN-γ-sensitive MKN45 cells. IFN-γ-induced growth inhibition and apoptosis in AGS cells were observed until galectin-3 expression was down-regulated. In the first part, these results demonstrate that an increase in galectin-3 facilitates AKT/GSK-3β/SHP2 signaling, causing cellular hyporesponsiveness to IFN-γ. Integrin-linked kinase (ILK), a serine/ threonine kinase, regulates cell adhesion, migration, and proliferation, also particularly by promoting AKT signaling. However, aberrant increased ILK did not affect AKT/GSK-3β and IFN-γ-activated IRF1, indicating ILK does not contribute to IFN-γ resistance. The role of ILK regulation is not clearly in AGS cells. Previous study shows that ILK increased in gastric cancer is correlated with tumor grade and metastasis. The regulation for ILK overexpression and mechanisms for ILK-regulated gastric tumorigenesis has not documented. We next want to identify the molecular basis for ILK regulation and its alternative role in the ERK1/2/NF-κB-mediated stimulation of proliferation, migration, and survival. Genetically or pharmacologically inhibiting ILK abolished NF-κB-regulated cell proliferation. Unpredictably, ILK stimulated Ras activity by facilitating the activation of c-Raf/MEK1/2/ERK1/2/ribosomal S6 kinase/inhibitor of κBα/NF-κB signaling by a complex of IQ motif containing GTPase activating protein (IQGAP) 1 and Ras. Enforced enzymatic ILK expression promoted cell proliferation by facilitating ERK1/2/NF-κB signaling. PI3K activation or the decreased expression of PTEN prolonged ERK1/2 activation through the protection of ILK from proteasome-mediated degradation. The C-terminus of heat shock cognate 70 interacting protein, a HSP90-associated E3 ubiquitin ligase, mediated ILK ubiquitination to control PI3K- and HSP90-regulated ILK stabilization and signaling. In addition to proliferation, this pathway also determined cell migration and restricted the sensitivity of anticancer agents to 5-fluorouracil and cisplatin. Additionally, validating EGF/EGFR signaling confirmed the ERK-regulatory roles of ILK and IQGAP1. These results demonstrate that an increase in ILK facilitates IQGAP1 and Ras interaction and non-canonically promotes ERK1/2/NF-κB activation to benefit cell growth. Taken together, we investigate IFN-γ susceptibility and oncogenic regulation in gastric cancer cells.

Abstract in English I
Abstract in Chinese III
Acknowledgement V
Abbreviations VI
Content X
Chapter 1 Introduction 1
1-1. Gastric cancer (epidemiology, risk factors and therapy)1
1-2 Hallmarks of cancer 2
1-2-1 Proliferating signaling 2
1-2-2 Somatic mutations activated signaling 3
1-2-3 Invading growth suppressors 4
1-2-4 Resisting cell death by oncogenic pathway 5
1-2-5 Avoiding immune destruction 6
2-1 Interferon-γ (IFN-γ) 7
2-1-1 IFN-γ signaling and negative-feedback regulators 8
2-1-2 IFN-γ affects cell growth and apoptosis 8
2-1-3 Molecules are involved in IFN-γ signaling	9
3-1 Galectins 10
3-1-1 Galectin-3 in apoptosis and tumorigenesis	11
4-1 Integrin-linked linase (ILK) 12
4-1-1 ILK signaling and its biofunctions 12
4-1-2 ILK activity and stability 13
Chapter 2 Objectives and Specific Aims 15
Chapter 3 17
An increase in galectin-3 causes cellular unresponsiveness to IFN-γ-induced signal transduction and growth inhibition in gastric cancer cells 17
3-1 Backgrounds and Specific Aims 17
3-2 Materials and Methods 19
3-2-1 Cell cultures and reagents 19
3-2-2 Plasmid transfection 19
3-2-3 Western blotting 20
3-2-4 Luciferase reporter assay 21
3-2-5 PI3K activity assay 21
3-2-6 Immunostaining 21
3-2-7 Lentiviral-based RNAi transfection 22
3-2-8 Cell growth assay 22
3-2-9 Cell apoptosis assay 22
3-2-10 Statistical analysis 23
3-3 Results 24
3-3-1 Increasing or decreasing galectin-3 expression affects IFN-γ signaling 24
3-3-2 Increased galectin-3 in cells shows cellular hyporesponsiveness to IFN-γ-activated IRF1 24
3-3-3 The pharmacological inhibition of extracellular galectin-3 does not affect IFN-γ resistance 25
3-3-4 IFN-γ-insensitive AGS cells show an increase in galectin-3 expression independent of deregulated PI3K and PTEN expression 25
3-3-5 Changing galectin-3 expression does not alter PI3K activity but affects AKT phosphorylation at the threonine residue 26
3-3-6 Decreased galectin-3 facilitates IFN-γ-mediated cell growth inhibition and apoptosis in AGS cells 27
3-4 Discussion 28
3-4-1 The IFN-γ signaling in galectin-3 regulation 28
3-4-2 The pro- or anti-apoptotic role in galectin-3 expression 29
3-4-3 The mechanism of galectin-3 expression in PI3K/AKT and GSK-3β signaling 30
3-5 Figures 32
Figure 3.1 Decreasing or increasing galectin-3 expression interferes IFN-γ signaling. 32
Figure 3.2 Inducible galectin-3 correlates to cellular insensitivity to IFN-γ. 33
Figure 3.3 No extracellular galectin-3 is involved in IFN-γ insensitivity of AGS cells. 34
Figure 3.4 An increased galectin-3 expression correlates to PI3K-AKT activation and PTEN decrease in IFN-γ insensitive AGS cells. 35
Figure 3.5 Galectin-3 facilitates AKT/GSK-3β/SHP2 signaling pathway downstream of PI3K and PDK1 activation and overexpression of AKT, inactive GSK-3β, and SHP2 suppress IFN-γ-activated IRF1. 36
Figure 3.6 Silencing galecin-3 sensitizes AGS cells to IFN-γ-induced cell growth inhibition and apoptosis. 38
Chapter 4 39
Molecular Regulation of ILK in Gastric Cancer Cells and Its Role in IFN-γ Susceptibility 39
4-1 Backgrounds and Specific Aims 39
4-2 Materials and Methods 41
4-2-1 Reagents and antibodies 41
4-2-2 Gastric cancer specimens 42
4-2-3 Cell lines and cell culture 42
4-2-4 Immunohistochemical/immunocytochemical staining 43
4-2-5 Colony forming assay 43
4-2-6 Lentiviral-based RNAi transfection 44
4-2-7 Electrophoretic mobility shift assays (EMSA) 45
4-2-8 Ras pull-down assay 46
4-2-9 Co-immunoprecipitation 46
4-2-10 Plasmid transfection 47
4-2-11 Wound healing assay 47
4-2-12 Cytotoxicity assay 47
4-2-13 Statistical analyses 48
4-3 Results 49
4-3-1 ILK does not activate AKT/GSK-3β signaling to regulate IFN-γ resistant in gastric AGS cells 49
4-3-2 Expression and activity of ILK is indispensable for NF-κB-regulated cell proliferation 49
4-3-3 ILK regulates Ras activity by sustaining the IQ motif containing GTPase activating protein (IQGAP) 1/Ras complex to control MAPK-activated NF-κB 50
4-3-4 Enzymatic ILK modulates IQGAP1/Ras complex formation and ERK1/2-mediated cell proliferation 52
4-3-5 PI3K activation and decreased PTEN facilitate ERK1/2/NF-κB activation by stabilizing ILK 53
4-3-6 PAK1 is required for c-Raf/ERK1/2- regulated NF-κB activation and cell proliferation, but not control ILK stabilization 54
4-3-7 HSP90-associated E3 ligase CHIP negatively controls ILK stabilization, ERK1/2/NF-κB activation, and cell proliferation 54
4-3-8 PI3K/HSP90/CHIP/ILK/IQGAP1/ERK1/2/NF-κB signaling contributes to cell migration and sensitivity to 5-FU and cisplatin 55
4-3-9 EGFR signaling regulates ILK/IQGAP1 to activate ERK1/2, NF-κB, cell migration, and proliferation 56
4-4 Discussion 57
4-4-1 The mechanism of ILK regulation in tumorigenesis 57
4-4-2 The relationship between ILK, IQGAP1, and Ras 57
4-4-3 ILK expression and stability in PI3K and HSP90 regulation 59
4-5 Figures 62
Figure 4.1 Aberrant expression of ILK does not contribute to the IFN-γ insensitivity in AGS cells. 62
Figure 4.2 ILK expression is required for cell proliferation. 63
Figure 4.3 ILK regulates NF-κB activation. 65
Figure 4.4 ILK facilitates ERK1/2 signaling. 67
Figure 4.5 IQGAP1 activates c-Raf/MEK1/2/ERK1/2/RSK/IκBα/NF-κB signaling. 69
Figure 4.6 ILK facilitates the formation of the IQGAP1/Ras complex to sustain Ras activity. 70
Figure 4.7 Enforced ILK expression facilitates cell proliferation by inducing ERK1/2/NF-κB activation. 71
Figure 4.8 Expression of integrins in AGS and MKN45 cells. 72
Figure 4.9 PI3K activation and PTEN loss facilitate ERK1/2/NF-κB activation through ILK stabilization. 73
Figure 4.10 PAK1 regulates for c-Raf/ERK1/2 signaling, NF-κB activation and cell proliferation but not for ILK stabilization. 74
Figure 4.11 AKT is not required for ILK stabilization in AGS cells. 75
Figure 4.12 CHIP determines ILK destabilization, ERK1/2/NF-κB inactivation, and cell growth inhibition after PI3K/HSP90 inactivation. 76
Figure 4.13 Signaling of PI3K/HSP90/CHIP/ILK/ERK1/2/NF-κB determines cell migration. 78
Figure 4.14 Signaling of PI3K/HSP90/CHIP/ILK/ERK1/2/NF-κB controls susceptibility to the anticancer agents 5-FU and cisplatin. 79
Figure 4.15 ILK and IQGAP1 facilitate EGF/EGFR-induced NF-κB activation, cell proliferation, and migration, and activated EGFR increases ILK expression. 80
Figure 4.16 ILK individually determines activation of AKT and ERK1/2 in response to different stimuli. 81
Figure 4.17 A hypothetical model for PI3K/HSP90-regulated ILK followed by ILK-facilitated IQGAP/Ras/c-Raf/MEK1/2/ERK1/2/RSK/NF-κB activation in cell proliferation, migration, and survival. 82
Chapter 5 Conclusion 83
Chapter 6 References 87
Appendix I. Gastric cancer incidence rates by sex in select registries. 102
Appendix II. Hallmarkers of cancer development. 103
Appendix III. The biofunctions of IFN-γ. 104
Appendix IV. AKT/GSK-3β/SHP2 controls IFN-γ signaling. 105
Appendix V. Galectin-3 regulates AKT activation. 106
Appendix VI. Integrin-linked kinase signaling and biofunctions. 107
Appendix VII. Integrin-linked kinase expression in human malignancies. 108
Curriculum vitae 109

                                    

Abril, E., Real, L.M., Serrano, A., Jimenez, P., Garcia, A., Canton, J., Trigo, I., Garrido, F., and Ruiz-Cabello, F. (1998). Unresponsiveness to interferon associated with STAT1 protein deficiency in a gastric adenocarcinoma cell line. Cancer immunology, immunotherapy : CII 47, 113-120.
Acconcia, F., Barnes, C.J., Singh, R.R., Talukder, A.H., and Kumar, R. (2007). Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase. Proceedings of the National Academy of Sciences of the United States of America 104, 6782-6787.
Agouni, A., Sourbier, C., Danilin, S., Rothhut, S., Lindner, V., Jacqmin, D., Helwig, J.J., Lang, H., and Massfelder, T. (2007). Parathyroid hormone-related protein induces cell survival in human renal cell carcinoma through the PI3K Akt pathway: evidence for a critical role for integrin-linked kinase and nuclear factor kappa B. Carcinogenesis 28, 1893-1901.
Akahani, S., Nangia-Makker, P., Inohara, H., Kim, H.R., and Raz, A. (1997). Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer research 57, 5272-5276.
Alberts, S.R., Cervantes, A., and van de Velde, C.J. (2003). Gastric cancer: epidemiology, pathology and treatment. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 14 Suppl 2, ii31-36.
Aoyagi, Y., Fujita, N., and Tsuruo, T. (2005). Stabilization of integrin-linked kinase by binding to Hsp90. Biochemical and biophysical research communications 331, 1061-1068.
Aviel-Ronen, S., Blackhall, F.H., Shepherd, F.A., and Tsao, M.S. (2006). K-ras mutations in non-small-cell lung carcinoma: a review. Clinical lung cancer 8, 30-38.
Ayhan, A., Yasui, W., Yokozaki, H., Seto, M., Ueda, R., and Tahara, E. (1994). Loss of heterozygosity at the bcl-2 gene locus and expression of bcl-2 in human gastric and colorectal carcinomas. Jpn J Cancer Res 85, 584-591.
Baldus, S.E., Zirbes, T.K., Weingarten, M., Fromm, S., Glossmann, J., Hanisch, F.G., Monig, S.P., Schroder, W., Flucke, U., Thiele, J., et al. (2000). Increased galectin-3 expression in gastric cancer: correlations with histopathological subtypes, galactosylated antigens and tumor cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21, 258-266.
Barondes, S.H., Cooper, D.N., Gitt, M.A., and Leffler, H. (1994). Galectins. Structure and function of a large family of animal lectins. J Biol Chem 269, 20807-20810.
Biron, C.A. (2001). Interferons alpha and beta as immune regulators--a new look. Immunity 14, 661-664.
Brenner, H., Rothenbacher, D., and Arndt, V. (2009). Epidemiology of stomach cancer. Methods in molecular biology 472, 467-477.
Brill, S., Li, S., Lyman, C.W., Church, D.M., Wasmuth, J.J., Weissbach, L., Bernards, A., and Snijders, A.J. (1996). The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases. Molecular and cellular biology 16, 4869-4878.
Cabodi, S., del Pilar Camacho-Leal, M., Di Stefano, P., and Defilippi, P. (2010). Integrin signalling adaptors: not only figurants in the cancer story. Nature reviews Cancer 10, 858-870.
Califice, S., Castronovo, V., and Van Den Brule, F. (2004). Galectin-3 and cancer (Review). Int J Oncol 25, 983-992.
Cantley, L.C., and Neel, B.G. (1999). New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proceedings of the National Academy of Sciences of the United States of America 96, 4240-4245.
Chan, G., Kalaitzidis, D., and Neel, B.G. (2008). The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer metastasis reviews 27, 179-192.
Chan, R.J., and Feng, G.S. (2007). PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase. Blood 109, 862-867.
Chang, Y.P., Tsai, C.C., Huang, W.C., Wang, C.Y., Chen, C.L., Lin, Y.S., Kai, J.I., Hsieh, C.Y., Cheng, Y.L., Choi, P.C., et al. (2010). Autophagy facilitates IFN-gamma-induced Jak2-STAT1 activation and cellular inflammation. J Biol Chem 285, 28715-28722. Chen, Z., Trotman, L.C., Shaffer, D., Lin, H.K., Dotan, Z.A., Niki, M., Koutcher, J.A., Scher, H.I., Ludwig, T., Gerald, W., et al. (2005). Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725-730.
Cheng, Y.L., Huang, W.C., Chen, C.L., Tsai, C.C., Wang, C.Y., Chiu, W.H., Chen, Y.L., Lin, Y.S., Chang, C.F., and Lin, C.F. (2011). Increased galectin-3 facilitates leukemia cell survival from apoptotic stimuli. Biochemical and biophysical research communications 412, 334-340.
Cheong, T.C., Shin, J.Y., and Chun, K.H. (2010). Silencing of galectin-3 changes the gene expression and augments the sensitivity of gastric cancer cells to chemotherapeutic agents. Cancer science 101, 94-102.
Cooper, D.N. (2002). Galectinomics: finding themes in complexity. Biochim Biophys Acta 1572, 209-231.
Cretney, E., Takeda, K., Yagita, H., Glaccum, M., Peschon, J.J., and Smyth, M.J. (2002). Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. Journal of immunology 168, 1356-1361.
D'Amico, M., Hulit, J., Amanatullah, D.F., Zafonte, B.T., Albanese, C., Bouzahzah, B., Fu, M., Augenlicht, L.H., Donehower, L.A., Takemaru, K., et al. (2000). The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP-responsive element-binding protein-dependent pathways. The Journal of biological chemistry 275, 32649-32657.
Dan, L., Jian, D., Na, L., and Xiaozhong, W. (2012). Crosstalk between EGFR and integrin affects invasion and proliferation of gastric cancer cell line, SGC7901. OncoTargets and therapy 5, 271-277.
Davies, M.A., and Samuels, Y. (2010). Analysis of the genome to personalize therapy for melanoma. Oncogene 29, 5545-5555.
De Luca, A., MacLachlan, T.K., Bagella, L., Dean, C., Howard, C.M., Claudio, P.P., Baldi, A., Khalili, K., and Giordano, A. (1997). A unique domain of pRb2/p130 acts as an inhibitor of Cdk2 kinase activity. J Biol Chem 272, 20971-20974.
Dedhar, S. (2000). Cell-substrate interactions and signaling through ILK. Current opinion in cell biology 12, 250-256.
Degiuli, M., Sasako, M., Ponti, A., Soldati, T., Danese, F., and Calvo, F. (1998). Morbidity and mortality after D2 gastrectomy for gastric cancer: results of the Italian Gastric Cancer Study Group prospective multicenter surgical study. J Clin Oncol 16, 1490-1493.
Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J., and Dedhar, S. (1998). Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase. Proceedings of the National Academy of Sciences of the United States of America 95, 11211-11216.
Ding, Q., He, X., Xia, W., Hsu, J.M., Chen, C.T., Li, L.Y., Lee, D.F., Yang, J.Y., Xie, X., Liu, J.C., et al. (2007). Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3beta activity and associates with poor prognosis in human breast cancer. Cancer Res 67, 4564-4571.
Dobreva, I., Fielding, A., Foster, L.J., and Dedhar, S. (2008). Mapping the integrin-linked kinase interactome using SILAC. Journal of proteome research 7, 1740-1749.
Donehower, L.A., Harvey, M., Slagle, B.L., McArthur, M.J., Montgomery, C.A., Jr., Butel, J.S., and Bradley, A. (1992). Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215-221.
Dumic, J., Dabelic, S., and Flogel, M. (2006). Galectin-3: an open-ended story. Biochim Biophys Acta 1760, 616-635.
Dumic, J., Lauc, G., and Flogel, M. (2000). Expression of galectin-3 in cells exposed to stress-roles of jun and NF-kappaB. Cell Physiol Biochem 10, 149-158.
Elad-Sfadia, G., Haklai, R., Balan, E., and Kloog, Y. (2004). Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity. The Journal of biological chemistry 279, 34922-34930.
Eldar-Finkelman, H., Seger, R., Vandenheede, J.R., and Krebs, E.G. (1995). Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. J Biol Chem 270, 987-990.
Emanuele, M.J., Elia, A.E., Xu, Q., Thoma, C.R., Izhar, L., Leng, Y., Guo, A., Chen, Y.N., Rush, J., Hsu, P.W., et al. (2011). Global identification of modular cullin-RING ligase substrates. Cell 147, 459-474.
Erez, N., Truitt, M., Olson, P., Arron, S.T., and Hanahan, D. (2010). Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer cell 17, 135-147.
Farrar, M.A., and Schreiber, R.D. (1993). The molecular cell biology of interferon-gamma and its receptor. Annual review of immunology 11, 571-611.
Forbes, S.A., Bindal, N., Bamford, S., Cole, C., Kok, C.Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011). COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 39, D945-950.
Frame, S., and Cohen, P. (2001). GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359, 1-16.
Froelich, C.J., Orth, K., Turbov, J., Seth, P., Gottlieb, R., Babior, B., Shah, G.M., Bleackley, R.C., Dixit, V.M., and Hanna, W. (1996). New paradigm for lymphocyte granule-mediated cytotoxicity. Target cells bind and internalize granzyme B, but an endosomolytic agent is necessary for cytosolic delivery and subsequent apoptosis. J Biol Chem 271, 29073-29079.
Fujita, N., Sato, S., Ishida, A., and Tsuruo, T. (2002). Involvement of Hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. The Journal of biological chemistry 277, 10346-10353.
Fukumori, T., Kanayama, H.O., and Raz, A. (2007). The role of galectin-3 in cancer drug resistance. Drug Resist Updat 10, 101-108.
Gaudin, J.C., Arar, C., Monsigny, M., and Legrand, A. (1997). Modulation of the expression of the rabbit galectin-3 gene by p53 and c-Ha-ras proteins and PMA. Glycobiology 7, 1089-1098.
Gollob, J.A., Sciambi, C.J., Huang, Z., and Dressman, H.K. (2005). Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-gamma. Cancer research 65, 8869-8877.
Graff, J.R., Deddens, J.A., Konicek, B.W., Colligan, B.M., Hurst, B.M., Carter, H.W., and Carter, J.H. (2001). Integrin-linked kinase expression increases with prostate tumor grade. Clinical cancer research : an official journal of the American Association for Cancer Research 7, 1987-1991.
Grimes, C.A., and Jope, R.S. (2001). The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol 65, 391-426.
Gryko, M., Pryczynicz, A., Zareba, K., Kedra, B., Kemona, A., and Guzinska-Ustymowicz, K. (2014). The expression of Bcl-2 and BID in gastric cancer cells. J Immunol Res 2014, 953203.
Gu, H., Maeda, H., Moon, J.J., Lord, J.D., Yoakim, M., Nelson, B.H., and Neel, B.G. (2000). New role for Shc in activation of the phosphatidylinositol 3-kinase/Akt pathway. Mol Cell Biol 20, 7109-7120.
Hannigan, G.E., Leung-Hagesteijn, C., Fitz-Gibbon, L., Coppolino, M.G., Radeva, G., Filmus, J., Bell, J.C., and Dedhar, S. (1996). Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 379, 91-96.
Harbour, J.W., and Dean, D.C. (2000). The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev 14, 2393-2409.
Harris, C.C., and Hollstein, M. (1993). Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329, 1318-1327.
Hart, M.J., Callow, M.G., Souza, B., and Polakis, P. (1996). IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. The EMBO journal 15, 2997-3005.
Hashiramoto, A., Murata, M., Kawazoe, T., Yoshida, K., Akiyama, C., Shiozawa, K., and Shiozawa, S. (2011). Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial cells by stabilizing integrin-linked kinase, extracellular signal-regulated kinase and protein kinase B. Rheumatology 50, 852-861.
Hatakeyama, M. (2004). Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 4, 688-694.
Heinrich, T., and Gloor, B. (1992). [Importance of standardized photos for planimetry]. Klin Monbl Augenheilkd 200, 289-291.
Hiyama, T., Haruma, K., Kitadai, Y., Masuda, H., Miyamoto, M., Tanaka, S., Yoshihara, M., Shimamoto, F., and Chayama, K. (2002). K-ras mutation in helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer. International journal of cancer Journal international du cancer 97, 562-566.
Horii, A., Nakatsuru, S., Miyoshi, Y., Ichii, S., Nagase, H., Kato, Y., Yanagisawa, A., and Nakamura, Y. (1992). The APC gene, responsible for familial adenomatous polyposis, is mutated in human gastric cancer. Cancer Res 52, 3231-3233.
Houghton, J., Fox, J.G., and Wang, T.C. (2002). Gastric cancer: laboratory bench to clinic. J Gastroenterol Hepatol 17, 495-502.
Hoyer, K.K., Pang, M., Gui, D., Shintaku, I.P., Kuwabara, I., Liu, F.T., Said, J.W., Baum, L.G., and Teitell, M.A. (2004). An anti-apoptotic role for galectin-3 in diffuse large B-cell lymphomas. Am J Pathol 164, 893-902.
Huang, P.H., Xu, A.M., and White, F.M. (2009). Oncogenic EGFR signaling networks in glioma. Sci Signal 2, re6.
Huang, Y., Li, J., Zhang, Y., and Wu, C. (2000). The roles of integrin-linked kinase in the regulation of myogenic differentiation. The Journal of cell biology 150, 861-872.
Hundahl, S.A., Menck, H.R., Mansour, E.G., and Winchester, D.P. (1997). The National Cancer Data Base report on gastric carcinoma. Cancer 80, 2333-2341.
Ito, R., Oue, N., Zhu, X., Yoshida, K., Nakayama, H., Yokozaki, H., and Yasui, W. (2003). Expression of integrin-linked kinase is closely correlated with invasion and metastasis of gastric carcinoma. Virchows Archiv : an international journal of pathology 442, 118-123.
Jameson, K.L., Mazur, P.K., Zehnder, A.M., Zhang, J., Zarnegar, B., Sage, J., and Khavari, P.A. (2013). IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nature medicine 19, 626-630.
Jemal, A., Center, M.M., DeSantis, C., and Ward, E.M. (2010). Global patterns of cancer incidence and mortality rates and trends. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19, 1893-1907.
Jeon, S.B., Yoon, H.J., Chang, C.Y., Koh, H.S., Jeon, S.H., and Park, E.J. (2010). Galectin-3 exerts cytokine-like regulatory actions through the JAK-STAT pathway. Journal of immunology 185, 7037-7046.
Jiang, B.H., and Liu, L.Z. (2009). PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res 102, 19-65.
Kano, A., Watanabe, Y., Takeda, N., Aizawa, S., and Akaike, T. (1997). Analysis of IFN-gamma-induced cell cycle arrest and cell death in hepatocytes. J Biochem 121, 677-683.
Kaplan, D.H., Shankaran, V., Dighe, A.S., Stockert, E., Aguet, M., Old, L.J., and Schreiber, R.D. (1998). Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proceedings of the National Academy of Sciences of the United States of America 95, 7556-7561.
Karakas, B., Bachman, K.E., and Park, B.H. (2006). Mutation of the PIK3CA oncogene in human cancers. Br J Cancer 94, 455-459.
Katoh, M. (2007). Dysregulation of stem cell signaling network due to germline mutation, SNP, Helicobacter pylori infection, epigenetic change and genetic alteration in gastric cancer. Cancer Biol Ther 6, 832-839.
Kayagaki, N., Yamaguchi, N., Nakayama, M., Takeda, K., Akiba, H., Tsutsui, H., Okamura, H., Nakanishi, K., Okumura, K., and Yagita, H. (1999). Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells. Journal of immunology 163, 1906-1913.
Ke, J.J., Shao, Q.S., and Ling, Z.Q. (2006). Expression of E-selectin, integrin beta1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance. World journal of gastroenterology : WJG 12, 3609-3611.
Kim, H.R., Lin, H.M., Biliran, H., and Raz, A. (1999). Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer research 59, 4148-4154.
Kim, K., Mayer, E.P., and Nachtigal, M. (2003). Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins. Biochim Biophys Acta 1641, 13-23.
Kim, S.J., Choi, I.J., Cheong, T.C., Lee, S.J., Lotan, R., Park, S.H., and Chun, K.H. (2010). Galectin-3 increases gastric cancer cell motility by up-regulating fascin-1 expression. Gastroenterology 138, 1035-1045 e1031-1032.
Kim, S.J., Shin, J.Y., Cheong, T.C., Choi, I.J., Lee, Y.S., Park, S.H., and Chun, K.H. (2011a). Galectin-3 germline variant at position 191 enhances nuclear accumulation and activation of beta-catenin in gastric cancer. Clin Exp Metastasis 28, 743-750.
Kim, S.J., Shin, J.Y., Lee, K.D., Bae, Y.K., Choi, I.J., Park, S.H., and Chun, K.H. (2011b). Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1) and matrix metalloproteinase-1 (MMP-1). PLoS One 6, e25103.
King, C.C., Gardiner, E.M., Zenke, F.T., Bohl, B.P., Newton, A.C., Hemmings, B.A., and Bokoch, G.M. (2000). p21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). The Journal of biological chemistry 275, 41201-41209.
Klein, G. (2004). Cancer, apoptosis, and nonimmune surveillance. Cell Death Differ 11, 13-17.
Klein, R., Vollmers, H., and Mullerhermelink, H. (1996). Different expression of Bcl-2 in diffuse and intestinal type stomach carcinomas. Oncol Rep 3, 825-828.
Knoll, R., Postel, R., Wang, J., Kratzner, R., Hennecke, G., Vacaru, A.M., Vakeel, P., Schubert, C., Murthy, K., Rana, B.K., et al. (2007). Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation 116, 515-525.
Lang, S.A., Gaumann, A., Koehl, G.E., Seidel, U., Bataille, F., Klein, D., Ellis, L.M., Bolder, U., Hofstaedter, F., Schlitt, H.J., et al. (2007). Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120, 1803-1810.
Le Bon, A., and Tough, D.F. (2002). Links between innate and adaptive immunity via type I interferon. Curr Opin Immunol 14, 432-436.
Lee, S.L., Hsu, E.C., Chou, C.C., Chuang, H.C., Bai, L.Y., Kulp, S.K., and Chen, C.S. (2011). Identification and characterization of a novel integrin-linked kinase inhibitor. Journal of medicinal chemistry 54, 6364-6374.
Leffler, H., Carlsson, S., Hedlund, M., Qian, Y., and Poirier, F. (2004). Introduction to galectins. Glycoconj J 19, 433-440.
Lehtonen, A., Matikainen, S., and Julkunen, I. (1997). Interferons up-regulate STAT1, STAT2, and IRF family transcription factor gene expression in human peripheral blood mononuclear cells and macrophages. J Immunol 159, 794-803.
Leung, W.K., Wu, M.S., Kakugawa, Y., Kim, J.J., Yeoh, K.G., Goh, K.L., Wu, K.C., Wu, D.C., Sollano, J., Kachintorn, U., et al. (2008). Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol 9, 279-287.
Levine, A.J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.
Liang, C.H., Chiu, S.Y., Hsu, I.L., Wu, Y.Y., Tsai, Y.T., Ke, J.Y., Pan, S.H., Hsu, Y.C., Li, K.C., Yang, P.C., et al. (2013a). alpha-Catulin drives metastasis by activating ILK and driving an alphavbeta3 integrin signaling axis. Cancer research 73, 428-438.
Liang, F., Zhang, S., Wang, B., Qiu, J., and Wang, Y. (2013b). Overexpression of integrin-linked kinase (ILK) promotes glioma cell invasion and migration and down-regulates E-cadherin via the NF-kappaB pathway. Journal of molecular histology.
Lin, H.M., Pestell, R.G., Raz, A., and Kim, H.R. (2002). Galectin-3 enhances cyclin D(1) promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells. Oncogene 21, 8001-8010.
Liu, F.T., Patterson, R.J., and Wang, J.L. (2002). Intracellular functions of galectins. Biochim Biophys Acta 1572, 263-273.
Liu, H., Dibling, B., Spike, B., Dirlam, A., and Macleod, K. (2004). New roles for the RB tumor suppressor protein. Curr Opin Genet Dev 14, 55-64.
Luo, R.X., Postigo, A.A., and Dean, D.C. (1998). Rb interacts with histone deacetylase to repress transcription. Cell 92, 463-473.
Madrid, L.V., Mayo, M.W., Reuther, J.Y., and Baldwin, A.S., Jr. (2001). Akt stimulates the transactivation potential of the RelA/p65 Subunit of NF-kappa B through utilization of the Ikappa B kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem 276, 18934-18940.
Madrid, L.V., Wang, C.Y., Guttridge, D.C., Schottelius, A.J., Baldwin, A.S., Jr., and Mayo, M.W. (2000). Akt suppresses apoptosis by stimulating the transactivation potential of the RelA/p65 subunit of NF-kappaB. Mol Cell Biol 20, 1626-1638.
Makino, K., Day, C.P., Wang, S.C., Li, Y.M., and Hung, M.C. (2004). Upregulation of IKKalpha/IKKbeta by integrin-linked kinase is required for HER2/neu-induced NF-kappaB antiapoptotic pathway. Oncogene 23, 3883-3887.
Malkin, D., Li, F.P., Strong, L.C., Fraumeni, J.F., Jr., Nelson, C.E., Kim, D.H., Kassel, J., Gryka, M.A., Bischoff, F.Z., Tainsky, M.A., et al. (1990). Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250, 1233-1238.
Malmberg, K.J., and Ljunggren, H.G. (2006). Escape from immune- and nonimmune-mediated tumor surveillance. Seminars in cancer biology 16, 16-31.
Malumbres, M., and Barbacid, M. (2003). RAS oncogenes: the first 30 years. Nature reviews Cancer 3, 459-465.
Marth, C., Windbichler, G.H., Hausmaninger, H., Petru, E., Estermann, K., Pelzer, A., and Mueller-Holzner, E. (2006). Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study. Int J Gynecol Cancer 16, 1522-1528.
Maurer, U., Charvet, C., Wagman, A.S., Dejardin, E., and Green, D.R. (2006). Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell 21, 749-760.
McCubrey, J.A., Steelman, L.S., Abrams, S.L., Lee, J.T., Chang, F., Bertrand, F.E., Navolanic, P.M., Terrian, D.M., Franklin, R.A., D'Assoro, A.B., et al. (2006). Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul 46, 249-279.
McDonald, P.C., Fielding, A.B., and Dedhar, S. (2008). Integrin-linked kinase--essential roles in physiology and cancer biology. Journal of cell science 121, 3121-3132.
Medici, D., and Nawshad, A. (2010). Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent activation of NF-kappaB and LEF-1. Matrix biology : journal of the International Society for Matrix Biology 29, 161-165.
Mendonca, D.F., Chammas, R., Liu, F.T., Nonogaki, S., Cardoso, S.V., Loyola, A.M., and de Faria, P.R. (2012). The inactive form of glycogen synthase kinase-3beta is associated with the development of carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice. International journal of clinical and experimental pathology 5, 547-554.
Meyer-ter-Vehn, T., Covacci, A., Kist, M., and Pahl, H.L. (2000). Helicobacter pylori activates mitogen-activated protein kinase cascades and induces expression of the proto-oncogenes c-fos and c-jun. The Journal of biological chemistry 275, 16064-16072.
Miller, C.H., Maher, S.G., and Young, H.A. (2009). Clinical Use of Interferon-gamma. Annals of the New York Academy of Sciences 1182, 69-79.
Miyazaki, J., Hokari, R., Kato, S., Tsuzuki, Y., Kawaguchi, A., Nagao, S., Itoh, K., and Miura, S. (2002). Increased expression of galectin-3 in primary gastric cancer and the metastatic lymph nodes. Oncol Rep 9, 1307-1312.
Morimoto, A.M., Tomlinson, M.G., Nakatani, K., Bolen, J.B., Roth, R.A., and Herbst, R. (2000). The MMAC1 tumor suppressor phosphatase inhibits phospholipase C and integrin-linked kinase activity. Oncogene 19, 200-209.
Moul, J.W., Friedrichs, P.A., Lance, R.S., Theune, S.M., and Chang, E.H. (1992). Infrequent RAS oncogene mutations in human prostate cancer. The Prostate 20, 327-338.
Murata, S., Minami, Y., Minami, M., Chiba, T., and Tanaka, K. (2001). CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO reports 2, 1133-1138.
Nakahara, S., Oka, N., and Raz, A. (2005). On the role of galectin-3 in cancer apoptosis. Apoptosis 10, 267-275.
Nakayama, M., Hisatsune, J., Yamasaki, E., Isomoto, H., Kurazono, H., Hatakeyama, M., Azuma, T., Yamaoka, Y., Yahiro, K., Moss, J., et al. (2009). Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway. The Journal of biological chemistry 284, 1612-1619.
Noguchi, S., Yasui, Y., Iwasaki, J., Kumazaki, M., Yamada, N., Naito, S., and Akao, Y. (2013). Replacement treatment with microRNA-143 and -145 induces synergistic inhibition of the growth of human bladder cancer cells by regulating PI3K/Akt and MAPK signaling pathways. Cancer letters 328, 353-361.
Normanno, N., De Luca, A., Bianco, C., Strizzi, L., Mancino, M., Maiello, M.R., Carotenuto, A., De Feo, G., Caponigro, F., and Salomon, D.S. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366, 2-16.
Ochieng, J., Furtak, V., and Lukyanov, P. (2004). Extracellular functions of galectin-3. Glycoconj J 19, 527-535.
Oka, N., Nakahara, S., Takenaka, Y., Fukumori, T., Hogan, V., Kanayama, H.O., Yanagawa, T., and Raz, A. (2005). Galectin-3 inhibits tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by activating Akt in human bladder carcinoma cells. Cancer research 65, 7546-7553.
Osaki, M., Oshimura, M., and Ito, H. (2004). PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9, 667-676.
Parmar, S., and Platanias, L.C. (2003). Interferons: mechanisms of action and clinical applications. Current opinion in oncology 15, 431-439.
Persad, S., Attwell, S., Gray, V., Delcommenne, M., Troussard, A., Sanghera, J., and Dedhar, S. (2000). Inhibition of integrin-linked kinase (ILK) suppresses activation of protein kinase B/Akt and induces cell cycle arrest and apoptosis of PTEN-mutant prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America 97, 3207-3212.
Persad, S., Attwell, S., Gray, V., Mawji, N., Deng, J.T., Leung, D., Yan, J., Sanghera, J., Walsh, M.P., and Dedhar, S. (2001). Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. The Journal of biological chemistry 276, 27462-27469.
Persad, S., and Dedhar, S. (2003). The role of integrin-linked kinase (ILK) in cancer progression. Cancer metastasis reviews 22, 375-384.
Pestka, S. (1987). Advances in cancer: interferon--achievements and potential. N J Med 84, 51-56.
Platanias, L.C. (2005). Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5, 375-386.
Prior, I.A., Lewis, P.D., and Mattos, C. (2012). A comprehensive survey of Ras mutations in cancer. Cancer research 72, 2457-2467.
Radovanac, K., Morgner, J., Schulz, J.N., Blumbach, K., Patterson, C., Geiger, T., Mann, M., Krieg, T., Eckes, B., Fassler, R., et al. (2013). Stabilization of integrin-linked kinase by the Hsp90-CHIP axis impacts cellular force generation, migration and the fibrotic response. The EMBO journal 32, 1409-1424.
Raimond, J., Rouleux, F., Monsigny, M., and Legrand, A. (1995). The second intron of the human galectin-3 gene has a strong promoter activity down-regulated by p53. FEBS letters 363, 165-169.
Ramos, J.W. (2008). The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. The international journal of biochemistry & cell biology 40, 2707-2719.
Ravi, R., and Bedi, A. (2004). NF-kappaB in cancer--a friend turned foe. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 7, 53-67.
Rayasam, G.V., Tulasi, V.K., Sodhi, R., Davis, J.A., and Ray, A. (2009). Glycogen synthase kinase 3: more than a namesake. Br J Pharmacol 156, 885-898.
Resende, C., Ristimaki, A., and Machado, J.C. (2010). Genetic and epigenetic alteration in gastric carcinogenesis. Helicobacter 15 Suppl 1, 34-39.
Roy, M., Li, Z., and Sacks, D.B. (2005). IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Molecular and cellular biology 25, 7940-7952.
Samuel, C.E. (2001). Antiviral actions of interferons. Clin Microbiol Rev 14, 778-809, table of contents.
Sato, S., Fujita, N., and Tsuruo, T. (2000). Modulation of Akt kinase activity by binding to Hsp90. Proceedings of the National Academy of Sciences of the United States of America 97, 10832-10837.
Schroder, K., Hertzog, P.J., Ravasi, T., and Hume, D.A. (2004). Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75, 163-189.
Schulte, T.W., Blagosklonny, M.V., Ingui, C., and Neckers, L. (1995). Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association. The Journal of biological chemistry 270, 24585-24588.
Shalom-Feuerstein, R., Cooks, T., Raz, A., and Kloog, Y. (2005). Galectin-3 regulates a molecular switch from N-Ras to K-Ras usage in human breast carcinoma cells. Cancer research 65, 7292-7300.
Shankaran, V., Ikeda, H., Bruce, A.T., White, J.M., Swanson, P.E., Old, L.J., and Schreiber, R.D. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107-1111.
Shi, L., Mai, S., Israels, S., Browne, K., Trapani, J.A., and Greenberg, A.H. (1997). Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization. The Journal of experimental medicine 185, 855-866.
Shimura, T., Takenaka, Y., Fukumori, T., Tsutsumi, S., Okada, K., Hogan, V., Kikuchi, A., Kuwano, H., and Raz, A. (2005). Implication of galectin-3 in Wnt signaling. Cancer research 65, 3535-3537.
Shuai, K., and Liu, B. (2003). Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3, 900-911.
Siewert, J.R., Bottcher, K., Roder, J.D., Busch, R., Hermanek, P., and Meyer, H.J. (1993). Prognostic relevance of systematic lymph node dissection in gastric carcinoma. German Gastric Carcinoma Study Group. Br J Surg 80, 1015-1018.
Singh, S.S., Yap, W.N., Arfuso, F., Kar, S., Wang, C., Cai, W., Dharmarajan, A.M., Sethi, G., and Kumar, A.P. (2015). Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine? World J Gastroenterol 21, 12261-12273.
Smyth, M.J., and Godfrey, D.I. (2000). NKT cells and tumor immunity--a double-edged sword. Nat Immunol 1, 459-460.
Smyth, M.J., Thia, K.Y., Street, S.E., MacGregor, D., Godfrey, D.I., and Trapani, J.A. (2000). Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. The Journal of experimental medicine 192, 755-760.
Song, M.M., and Shuai, K. (1998). The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem 273, 35056-35062.
Song, S., Ji, B., Ramachandran, V., Wang, H., Hafley, M., Logsdon, C., and Bresalier, R.S. (2012). Overexpressed galectin-3 in pancreatic cancer induces cell proliferation and invasion by binding Ras and activating Ras signaling. PLoS One 7, e42699.
Song, S., Mazurek, N., Liu, C., Sun, Y., Ding, Q.Q., Liu, K., Hung, M.C., and Bresalier, R.S. (2009). Galectin-3 mediates nuclear beta-catenin accumulation and Wnt signaling in human colon cancer cells by regulation of glycogen synthase kinase-3beta activity. Cancer research 69, 1343-1349.
Sonoda, Y., Watanabe, S., Matsumoto, Y., Aizu-Yokota, E., and Kasahara, T. (1999). FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma cell line. J Biol Chem 274, 10566-10570.
Souma, Y., Nishida, T., Serada, S., Iwahori, K., Takahashi, T., Fujimoto, M., Ripley, B., Nakajima, K., Miyazaki, Y., Mori, M., et al. (2012). Antiproliferative effect of SOCS-1 through the suppression of STAT3 and p38 MAPK activation in gastric cancer cells. International journal of cancer Journal international du cancer 131, 1287-1296.
Soutto, M., Belkhiri, A., Piazuelo, M.B., Schneider, B.G., Peng, D., Jiang, A., Washington, M.K., Kokoye, Y., Crowe, S.E., Zaika, A., et al. (2011). Loss of TFF1 is associated with activation of NF-kappaB-mediated inflammation and gastric neoplasia in mice and humans. J Clin Invest 121, 1753-1767.
Stemmermann, G., Heffelfinger, S.C., Noffsinger, A., Hui, Y.Z., Miller, M.A., and Fenoglio-Preiser, C.M. (1994). The molecular biology of esophageal and gastric cancer and their precursors: oncogenes, tumor suppressor genes, and growth factors. Hum Pathol 25, 968-981.
Street, S.E., Cretney, E., and Smyth, M.J. (2001). Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97, 192-197.
Street, S.E., Trapani, J.A., MacGregor, D., and Smyth, M.J. (2002). Suppression of lymphoma and epithelial malignancies effected by interferon gamma. The Journal of experimental medicine 196, 129-134.
Su, L.H., Chiu, C.H., Kuo, A.J., Chia, J.H., Sun, C.F., Leu, H.S., and Wu, T.L. (2001). Secular trends in incidence and antimicrobial resistance among clinical isolates of Salmonella at a university hospital in Taiwan, 1983-1999. Epidemiol Infect 127, 207-213.
Takanami, I. (2005). Increased expression of integrin-linked kinase is associated with shorter survival in non-small cell lung cancer. BMC cancer 5, 1.
Takatsuki, H., Komatsu, S., Sano, R., Takada, Y., and Tsuji, T. (2004). Adhesion of gastric carcinoma cells to peritoneum mediated by alpha3beta1 integrin (VLA-3). Cancer research 64, 6065-6070.
Takeda, K., Smyth, M.J., Cretney, E., Hayakawa, Y., Kayagaki, N., Yagita, H., and Okumura, K. (2002). Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. The Journal of experimental medicine 195, 161-169.
Tamura, G. (2006). Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer. World J Gastroenterol 12, 192-198.
Tang, C.K., Gong, X.Q., Moscatello, D.K., Wong, A.J., and Lippman, M.E. (2000). Epidermal growth factor receptor vIII enhances tumorigenicity in human breast cancer. Cancer research 60, 3081-3087.
Tsai, C.C., Kai, J.I., Huang, W.C., Wang, C.Y., Wang, Y., Chen, C.L., Fang, Y.T., Lin, Y.S., Anderson, R., Chen, S.H., et al. (2009). Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. Journal of immunology 183, 856-864.
Tseng, P.C., Chen, C.L., Shan, Y.S., Chang, W.T., Liu, H.S., Hong, T.M., Hsieh, C.Y., Lin, S.H., and Lin, C.F. (2014). An increase in integrin-linked kinase non-canonically confers NF- inverted question markB-mediated growth advantages to gastric cancer cells by activating ERK1/2. Cell communication and signaling : CCS 12, 69.
Tseng, P.C., Huang, W.C., Chen, C.L., Sheu, B.S., Shan, Y.S., Tsai, C.C., Wang, C.Y., Chen, S.O., Hsieh, C.Y., and Lin, C.F. (2012). Regulation of SHP2 by PTEN/AKT/GSK-3beta signaling facilitates IFN-gamma resistance in hyperproliferating gastric cancer. Immunobiology 217, 926-934.
van den Broek, M.E., Kagi, D., Ossendorp, F., Toes, R., Vamvakas, S., Lutz, W.K., Melief, C.J., Zinkernagel, R.M., and Hengartner, H. (1996). Decreased tumor surveillance in perforin-deficient mice. The Journal of experimental medicine 184, 1781-1790.
Walch, A., Seidl, S., Hermannstadter, C., Rauser, S., Deplazes, J., Langer, R., von Weyhern, C.H., Sarbia, M., Busch, R., Feith, M., et al. (2008). Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21, 544-552.
Wani, A.A., Jafarnejad, S.M., Zhou, J., and Li, G. (2011). Integrin-linked kinase regulates melanoma angiogenesis by activating NF-kappaB/interleukin-6 signaling pathway. Oncogene 30, 2778-2788.
Weinberg, R.A. (1995). The retinoblastoma protein and cell cycle control. Cell 81, 323-330.
White, C.D., Erdemir, H.H., and Sacks, D.B. (2012). IQGAP1 and its binding proteins control diverse biological functions. Cellular signalling 24, 826-834.
Wickstrom, S.A., Lange, A., Hess, M.W., Polleux, J., Spatz, J.P., Kruger, M., Pfaller, K., Lambacher, A., Bloch, W., Mann, M., et al. (2010). Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae. Developmental cell 19, 574-588.
Windbichler, G.H., Hausmaninger, H., Stummvoll, W., Graf, A.H., Kainz, C., Lahodny, J., Denison, U., Muller-Holzner, E., and Marth, C. (2000). Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer 82, 1138-1144.
Wu, C., and Dedhar, S. (2001). Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. The Journal of cell biology 155, 505-510.
Wu, X., Senechal, K., Neshat, M.S., Whang, Y.E., and Sawyers, C.L. (1998). The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proceedings of the National Academy of Sciences of the United States of America 95, 15587-15591.
Yang, R.Y., Hsu, D.K., and Liu, F.T. (1996). Expression of galectin-3 modulates T-cell growth and apoptosis. Proceedings of the National Academy of Sciences of the United States of America 93, 6737-6742.
Yang, R.Y., Rabinovich, G.A., and Liu, F.T. (2008). Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 10, e17.
Yoganathan, N., Yee, A., Zhang, Z., Leung, D., Yan, J., Fazli, L., Kojic, D.L., Costello, P.C., Jabali, M., Dedhar, S., et al. (2002). Integrin-linked kinase, a promising cancer therapeutic target: biochemical and biological properties. Pharmacol Ther 93, 233-242.
Yoon, Y.K., Kim, H.P., Han, S.W., Hur, H.S., Oh do, Y., Im, S.A., Bang, Y.J., and Kim, T.Y. (2009). Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells. Molecular cancer therapeutics 8, 2526-2536.
You, M., Yu, D.H., and Feng, G.S. (1999). Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway. Mol Cell Biol 19, 2416-2424.
Yuan, T.L., and Cantley, L.C. (2008). PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497-5510.
Zamai, L., Mariani, A.R., Zauli, G., Rodella, L., Rezzani, R., Manzoli, F.A., and Vitale, M. (1998). Kinetics of in vitro natural killer activity against K562 cells as detected by flow cytometry. Cytometry 32, 280-285.
Zeng, Y., Danielson, K.G., Albert, T.J., Shapiro, I.M., and Risbud, M.V. (2007). HIF-1 alpha is a regulator of galectin-3 expression in the intervertebral disc. J Bone Miner Res 22, 1851-1861.
Zhang, Y., Chen, K., Tu, Y., and Wu, C. (2004). Distinct roles of two structurally closely related focal adhesion proteins, alpha-parvins and beta-parvins, in regulation of cell morphology and survival. The Journal of biological chemistry 279, 41695-41705.
Zhao, G., Guo, L.L., Xu, J.Y., Yang, H., Huang, M.X., and Xiao, G. (2011). Integrin-linked kinase in gastric cancer cell attachment, invasion and tumor growth. World journal of gastroenterology : WJG 17, 3487-3496.
Zhao, M., Gao, Y., Wang, L., Liu, S., Han, B., Ma, L., Ling, Y., Mao, S., and Wang, X. (2013). Overexpression of integrin-linked kinase promotes lung cancer cell migration and invasion via NF-kappaB-mediated upregulation of matrix metalloproteinase-9. International journal of medical sciences 10, 995-1002.
Zheng, H.C., Xu, X.Y., Xia, P., Yu, M., Takahashi, H., and Takano, Y. (2010). Involvement of inactive GSK3beta overexpression in tumorigenesis and progression of gastric carcinomas. Hum Pathol 41, 1255-1264.
Zhou, Y., Weyman, C.M., Liu, H., Almasan, A., and Zhou, A. (2008). IFN-gamma induces apoptosis in HL-60 cells through decreased Bcl-2 and increased Bak expression. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 28, 65-72.
Zuehlke, A., and Johnson, J.L. (2010). Hsp90 and co-chaperones twist the functions of diverse client proteins. Biopolymers 93, 211-217.

校內：2021-02-01公開
校外：2021-02-01公開

簡易檢索 / 詳目顯示

相關論文