肺癌目前是全世界最普遍的一種惡性腫瘤，並且其發生率以及死亡率上升的速度也遠高於任何一種癌症。對於癌症病人來說，最主要面臨到的問題便是癌細胞的轉移，約有90 %的癌症病人是死於癌細胞的轉移，因而使得抑制轉移成為迫切的議題。然而目前在癌症治療上多半藉由藥物的細胞毒殺作用來達到治療癌症的目的，但此也是副作用產生的根本原因，因此若能減低藥物的使用劑量且抑制癌細胞轉移，將能減低藥物的副作用並有效延長癌症病人的壽命。過去以來廣泛認為癌細胞與其所轉移的臟器之間存在特異性，近年來的許多研究成果也均支持癌細胞是透過其表面特定分子和目標器官交互作用進而轉移。本篇研究所探討的纖連蛋白（Fibonectin）為一種多功能的醣蛋白，目前已有研究證實癌細胞表面所組裝的多聚體纖連蛋白（Polymeric fibronectin）會促進癌細胞特異性轉移至肺臟。本實驗首先由四種天然物中篩選出紫檀芪（Pterostilbene）抑制癌細胞表面多聚體纖連蛋白的效果最為顯著。紫檀芪最早是從紫檀木（P. santa-linus）中發現並分離出來的天然物，具有抗氧化、抗發炎、抗癌、抗轉移以及降血脂的活性。然而，紫檀芪在抗肺臟轉移的功效仍然尚未被探討，因此在本研究中，期望藉由使用紫檀芪抑制肺癌細胞表面多聚體纖連蛋白，進而抑制肺癌細胞轉移至肺臟。在細胞實驗的部分，使用Lewis Lung Carcinoma（LLC）cells，以免疫螢光染色觀察癌細胞表面多聚體纖連蛋白，利用Wound-healing assay、Transwell migration assay 以及Matrigel invasion assay 觀察肺癌細胞移行（migration）
與侵蝕（invasion）能力，並藉由西方墨點法分析相關蛋白表現；動物實驗則藉由C57BL/6 小鼠Lewis Lung Carcinoma-bearing Mouse Model，評估紫檀芪可能的抗肺臟轉移功效。研究結果首先以動物實驗確認纖連蛋白與肺臟轉移之相關性，證實當纖連蛋白被抑制後，會降低LLC cells 的肺臟轉移。接著發現紫檀芪可在未影響癌細胞後續存活率的濃度下（紫檀芪100 μM 以下處理四小時），顯著抑制癌細胞表面多聚體纖連蛋白的表現量，但並未抑制癌細胞日後的移行以及侵蝕能力。利用膜質分離，發現紫檀芪可抑制癌細胞表面多聚體纖連蛋白的組裝。紫檀芪會透過增加癌細胞pAkt的表現量及降低pERK 的表現量，降低纖連蛋白的組裝。進一步，將處理紫檀芪而降低表面多聚體纖連蛋白的癌細胞，以尾靜脈打入C57BL/6 小鼠體內，發現相較於未給藥組確實會降低肺癌細胞肺臟轉移的能力，並延長老鼠的存活天數。因此綜合以上研究結果顯示透過抑制纖連蛋白，紫檀芪對於抑制肺癌細胞的肺臟轉移將會是一種很有潛力的藥物。

Lung cancer is currently the most prevalent malignant tumor worldwide and has the fastest rising incidence and mortality rate of any cancer. The major problem for cancer patients is metastasis. The metastatic spread of cancer causes 90 % of human cancer deaths. Therefore, interfering metastasis may become the urgent subject. However, in the present, most of the cancer therapy used cytotoxic drugs, which induced severe side effects of cancer patients. Hence, using the lower doses of drugs, which also effectively inhibit metastasis may decrease side effects and prolong the lifespan of cancer patients. It has been suggested for a long time that tumor cells metastasize to its target organs with preferences, which is further supported that cancer cell selectively metastasize through the molecular on the surface of cancer cells interaction with their target organ. Fibronectin (FN) is a multifunctional glycoprotein. Recently, some researches supported that it is related with the polymeric fibronectin (polyFN) assembly on the surface of cancer cells and pulmonary metastasis. In this study, we first found the effect of pterostilbene in inhibiting polyFN was the most effective among four hydroxystilbenes. Pterostilbene was first isolated from P. santa-linus (red sandalwood), and has been shown diverse pharmacologic activities including antioxidant, anti-inflammation, anti-cancer, anti-metastasis and hypolipidemic activates. However, the effects of pterostilbene in anti-metastasis of lung cancer have not been studied. The aim of this study is to estimate the effects of pterostilbene in inhibiting pulmonary metastasis via suppressing polyFN assembly on the surface of blood-borne Lewis Lung Carcinoma（LLC）cells. In the In-vitro study, LLC cells was used and treated with pterostilbene in the end-over-end （EoE）suspension culture. Immunofluorescent staining was used to determine the polyFN assembly on the surface of LLC cells. Cell migration and invasion were determined by Wound-healing assay, Transwell migration assay and Matrigel invasion assay. The expression of proteins that related to polyFN assembly mechanisms were analyzed by Western blotting. In the In-vivo study, Lewis Lung Carcinoma-bearing Mouse Model in C57BL/6 mice was used to evaluate the possible anti-metastasis effects of pterostilbene. The results showed that FN knockdown inhibited LLC cells pulmonary metastasis in C57BL/6 mice. Pterostilbene did not reduce cell viability but significantly inhibited polyFN expression on the surface of suspended LLC cells（treated with pterostilbene under 100 μM for 4hrs）. Pterostilbene inhibited polyFN assembly through increasing Akt and decreasing ERK activity. In addition, pterostilbene treated LLC cells with lower polyFN assembly were injected into the lateral tail vein of C57BL/6 mice, and the results showed that pulmonary metastasis was significantly inhibited when compared with control group. Taken together, our study indicated that pterostilbene could be a promising agent in inhibiting lung metastasis through inhibition of polyFN assembly.

行政院衛生署。2010。台灣
何明霖。肺癌(Lung Cancer)醫療暨衛教網頁。彰化基督教醫院。台灣
何景良。鎖定標靶e 網打盡網頁。三軍總醫院 。台灣
何民康。標靶治療－大腸癌的最新用藥。郭綜合醫院。台灣
連熙隆。談肺癌之放射線治療。高雄醫學院放射治療學科。台灣
Adhami, V. M., Khan, N., and Mukhtar, H. (2009). Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer 61, 811-815.
Adrian, M., Jeandet, P., Douillet-Breuil, A. C., Tesson, L., and Bessis, R. (2000).Stilbene content of mature Vitis vinifera berries in response to UV-C elicitation. J Agric Food Chem 48, 6103-6105.
Al Moustafa, A. E., Alaoui-Jamali, M. A., Batist, G., Hernandez-Perez, M., Serruya, C., Alpert, L., Black, M. J., Sladek, R., and Foulkes, W. D. (2002). Identification of genes associated with head and neck carcinogenesis by cDNA microarray comparison between matched primary normal epithelial and squamous carcinoma cells. Oncogene 21, 2634-2640.
Bacac, M., and Stamenkovic, I. (2008). Metastatic cancer cell. Annu Rev Pathol 3, 221-247.
Benelli, R., Monteghirfo, S., Balbi, C., Barboro, P., and Ferrari, N. (2009). Novel antivascular efficacy of metronomic docetaxel therapy in prostate cancer: hnRNP K as a player. Int J Cancer 124, 2989-2996.
Bermudez, O., Pages, G., and Gimond, C. (2010). The dual-specificity MAP kinase phosphatases: critical roles in development and cancer. Am J Physiol Cell Physiol 299,
C189-202.
Bianchini, F., and Vainio, H. (2003). Wine and resveratrol: mechanisms of cancer prevention? Eur J Cancer Prev 12, 417-425.
Cavallaro, U., and Christofori, G. (2004). Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 4, 118-132.
Chakraborty, A., Gupta, N., Ghosh, K., and Roy, P. (2010). In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from
Pterocarpus marsupium. Toxicol In Vitro 24, 1215-1228.
Chen, R. J., Ho, C. T., and Wang, Y. J. (2010). Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. Mol Nutr Food Res 54, 1819-1832.
Cheng, H. C., Abdel-Ghany, M., Elble, R. C., and Pauli, B. U. (1998). Lung endothelial dipeptidyl peptidase IV promotes adhesion and metastasis of rat breast cancer cells via tumor cell surface-associated fibronectin. J Biol Chem 273, 24207-24215.
Cheng, H. C., Abdel-Ghany, M., and Pauli, B. U. (2003). A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis. J Biol Chem 278,
24600-24607.
Chiou, Y. S., Tsai, M. L., Wang, Y. J., Cheng, A. C., Lai, W. M., Badmaev, V., Ho, C. T., and Pan, M. H. (2010). Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice. J Agric Food Chem 58, 8833-8841.
Colvin, R. B. (1989). Fibronectin in wound healing. Academic Press. Danilkovitch, A., Skeel, A., and Leonard, E. J. (1999). Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism. Exp Cell Res 248, 575-582.
Ferrer, P., Asensi, M., Priego, S., Benlloch, M., Mena, S., Ortega, A., Obrador, E., Esteve, J. M., and Estrela, J. M. (2007). Nitric oxide mediates natural polyphenol-induced Bcl-2 down-regulation and activation of cell death in metastatic B16 melanoma. J Biol Chem 282, 2880-2890.
Ferrer, P., Asensi, M., Segarra, R., Ortega, A., Benlloch, M., Obrador, E., Varea, M. T., Asensio, G., Jorda, L., and Estrela, J. M. (2005). Asso ciation between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma. Neoplasia 7, 37-47.
Franke, T. F., Yang, S. I., Chan, T. O., Datta, K., Kazlauskas, A., Morrison, D. K., Kaplan, D. R., and Tsichlis, P. N. (1995). The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81, 727-736.
Friedl, P., and Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3, 362-374.
Guarino, M. (2007). Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol 39, 2153-2160.
Hood, J. D., and Cheresh, D. A. (2002). Role of integrins in cell invasion and migration. Nat Rev Cancer 2, 91-100.
Huang, L., Cheng, H. C., Isom, R., Chen, C. S., Levine, R. A., and Pauli, B. U. (2008).Protein kinase Cepsilon mediates polymeric fibronectin assembly on the surface of blood-borne rat breast cancer cells to promote pulmonary metastasis. J Biol Chem 283, 7616-7627.
Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W., Fong, H. H., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., et al. (1997). Cancer
chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218-220.
Jeong, S. H., Jo, W. S., Song, S., Suh, H., Seol, S. Y., Leem, S. H., Kwon, T. K., and Yoo, Y. H. (2009). A novel resveratrol derivative, HS1793, overcomes the resistance
conferred by Bcl-2 in human leukemic U937 cells. Biochem Pharmacol 77, 1337-1347.
Jung, D. B., Lee, H. J., Jeong, S. J., Lee, E. O., Kim, Y. C., Ahn, K. S., Chen, C. Y., and Kim, S. H. (2011). Rhapontigenin inhibited hypoxia inducible factor 1 alpha
accumulation and angiogenesis in hypoxic PC-3 prostate cancer cells. Biol Pharm Bull 34, 850-855.
Kapetanovic, I. M., Muzzio, M., Huang, Z., Thompson, T. N., and McCormick, D. L. (2010). Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and
its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol.
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., et al. (2005). VEGFR1-positive
haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820-827.
Kidera, Y., Tsubaki, M., Yamazoe, Y., Shoji, K., Nakamura, H., Ogaki, M., Satou, T., Itoh, T., Isozaki, M., Kaneko, J., et al. (2010). Reduction of lung metastasis, cell
invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway. J Exp Clin Cancer Res 29, 127.
Kim, J. K., Kim, N., and Lim, Y. H. (2010). Evaluation of the antibacterial activity of rhapontigenin produced from rhapontin by biotransformation against Propionibacterium
acnes. J Microbiol Biotechnol 20, 82-87.
Kim, Y. M., Yun, J., Lee, C. K., Lee, H., Min, K. R., and Kim, Y. (2002). Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of
action. J Biol Chem 277, 16340-16344.
Kimura, Y., and Okuda, H. (2001). Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr 131, 1844-1849.
L. Bavaresco, C. F., M.I. van Zeller de Macedo Basto Goncalves & S. Vezzulli (2009). Physiology & Molecular Biology Of Grapevine Stilbenes: An Update. Grapevine
Molecular Physiology & Biotechnology, 2nd edn, 341-364.
Langley, R. R., and Fidler, I. J. (2011). The seed and soil hypothesis revisited--the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128,
2527-2535.
Li, Y., Chen, Y., Tao, Y., Wang, Y., and Xu, W. (2011). Fibronectin increases RhoA activity through inhibition of PKA in the human gastric cancer cell line SGC-7901. Mol
Med Report 4, 65-69.
Lin, T., Zhang, L., Davis, J., Gu, J., Nishizaki, M., Ji, L., Roth, J. A., Xiong, M., and Fang, B. (2003). Combination of TRAIL gene therapy and chemotherapy enhances antitumor and antimetastasis effects in chemosensitive and chemoresistant breast cancers. Mol Ther 8, 441-448.
Mamon, H. J., Yeap, B. Y., Janne, P. A., Reblando, J., Shrager, S., Jaklitsch, M. T., Mentzer, S., Lukanich, J. M., Sugarbaker, D. J., Baldini, E. H., et al. (2005). High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation. J Clin Oncol 23, 1530-1537.
Mannal, P., McDonald, D., and McFadden, D. (2010a). Pterostilbene and tamoxifen show an additive effect against breast cancer in vitro. Am J Surg 200, 577-580.
Mannal, P. W., Alosi, J. A., Schneider, J. G., McDonald, D. E., and McFadden, D. W. (2010b). Pterostilbene inhibits pancreatic cancer in vitro. J Gastrointest Surg 14, 873-879.
Mao, Q. Q., Bai, Y., Lin, Y. W., Zheng, X. Y., Qin, J., Yang, K., and Xie, L. P. (2010). Resveratrol confers resistance against taxol via induction of cell cycle arrest in human cancer cell lines. Mol Nutr Food Res 54, 1574-1584.
Marrink, J., vd Geest, S., Sinnema, R., Vellenga, E., and de Vries, E. G. (1985). Fibronectin-complex (FN-C) present in normal plasma. Thromb Res 37, 689-692.
McGee, S. F., Lanigan, F., Gilligan, E., and Groner, B. (2006). Mammary gland biology and breast cancer. Conference on Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer Progression. EMBO Rep 7, 1084-1088.
Mikstacka, R., Rimando, A. M., and Ignatowicz, E. (2010). Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes
in vitro. Plant Foods Hum Nutr 65, 57-63.
Mulshine, J. L. (2005). New developments in lung cancer screening. J Clin Oncol 23, 3198-3202.
Neal, C. L., McKeithen, D., and Odero-Marah, V. A. (2011). Snail negatively regulates cell adhesion to extracellular matrix and integrin expression via the MAPK pathway in
prostate cancer cells. Cell Adh Migr 5.
Paget, S. (1889). The distribution of secondary growths in cancer of the breast. Lancet 1, 571-573.
Pan, M. H., Chang, Y. H., Badmaev, V., Nagabhushanam, K., and Ho, C. T. (2007). Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. J Agric Food Chem 55, 7777-7785.
Pan, M. H., Chiou, Y. S., Chen, W. J., Wang, J. M., Badmaev, V., and Ho, C. T. (2009). Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction
pathways in human hepatocellular carcinoma cells. Carcinogenesis 30, 1234-1242.
Park, E. S., Lim, Y., Hong, J. T., Yoo, H. S., Lee, C. K., Pyo, M. Y., and Yun, Y. P. (2010). Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway. Vascul Pharmacol 53, 61-67.
Perecko, T., Jancinova, V., Drabikova, K., Nosal, R., and Harmatha, J. (2008). Structure-efficiency relationship in derivatives of stilbene. Comparison of resveratrol,
pinosylvin and pterostilbene. Neuro Endocrinol Lett 29, 802-805.
Pussa, T., Raudsepp, P., Kuzina, K., and Raal, A. (2009). Polyphenolic composition of roots and petioles of Rheum rhaponticum L. Phytochem Anal 20, 98-103.
Remsberg, C. M., Yanez, J. A., Ohgami, Y., Vega-Villa, K. R., Rimando, A. M., and Davies, N. M. (2008). Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity.
Phytother Res 22, 169-179.
Rimando, A. M., Cuendet, M., Desmarchelier, C., Mehta, R. G., Pezzuto, J. M., and Duke, S. O. (2002). Cancer chemopreventive and antioxidant activities of pterostilbene,
a naturally occurring analogue of resveratrol. J Agric Food Chem 50, 3453-3457.
Rimando, A. M., and Suh, N. (2008). Biological/chemopreventive activity of stilbenes
and their effect on colon cancer. Planta Med 74, 1635-1643.
Ritzenthaler, J. D., Han, S., and Roman, J. (2008). Stimulation of lung carcinoma cell growth by fibronectin-integrin signalling. Mol Biosyst 4, 1160-1169.
Roupe, K. A., Remsberg, C. M., Yanez, J. A., and Davies, N. M. (2006). Pharmacometrics of stilbenes: seguing towards the clinic. Curr Clin Pharmacol 1, 81-101.
Ruoslahti, E. (1999). Fibronectin and its integrin receptors in cancer. Adv Cancer Res 76, 1-20.
Saiki, I. (1997). Cell adhesion molecules and cancer metastasis. Jpn J Pharmacol 75, 215-242.
Schafer, R. (1972). [The psychoanalytic view of reality. I]. Psyche (Stuttg) 26, 881-898.
Seger, R., and Krebs, E. G. (1995). The MAPK signaling cascade. FASEB J 9, 726-735.
Shin, N. H., Ryu, S. Y., Choi, E. J., Kang, S. H., Chang, I. M., Min, K. R., and Kim, Y.
(1998). Oxyresveratrol as the potent inhibitor on dopa oxidase activity of mushroom tyrosinase. Biochem Biophys Res Commun 243, 801-803.
Shukla, Y., and Singh, R. (2011). Resveratrol and cellular mechanisms of cancer prevention. Ann N Y Acad Sci 1215, 1-8.
Siemann, E., and Creasy, L. (1992). Concentration of phytoalexin resveratrol in wine. Am J Enol Vitic 43, 49-52.
Sobolev, V. S., Khan, S. I., Tabanca, N., Wedge, D. E., Manly, S. P., Cutler, S. J., Coy, M. R., Becnel, J. J., Neff, S. A., and Gloer, J. B. (2011). Biological activity of peanut (Arachis hypogaea) phytoalexins and selected natural and synthetic Stilbenoids. J Agric Food Chem 59, 1673-1682.
Song, H. P., Zhang, L., Dang, Y. M., Yan, H., Chu, Z. G., and Huang, Y. S. (2010). The phosphatidylinositol 3-kinase-Akt pathway protects cardiomyocytes from ischaemic and
hypoxic apoptosis via mitochondrial function. Clin Exp Pharmacol Physiol 37, 598-604.
Sporn, M. B. (1996). The war on cancer. Lancet 347, 1377-1381.
Stafford, L. J., Vaidya, K. S., and Welch, D. R. (2008). Metastasis suppressors genes in cancer. Int J Biochem Cell Biol 40, 874-891.
Stambolic, V., Mak, T. W., and Woodgett, J. R. (1999). Modulation of cellular apoptotic potential: contributions to oncogenesis. Oncogene 18, 6094-6103.
Stivala, L. A., Savio, M., Carafoli, F., Perucca, P., Bianchi, L., Maga, G., Forti, L., Pagnoni, U. M., Albini, A., Prosperi, E., and Vannini, V. (2001). Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J Biol Chem 276, 22586-22594.
Thompson, E. W., Newgreen, D. F., and Tarin, D. (2005). Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res 65, 5991-5995; discussion 5995.
Tolomeo, M., Grimaudo, S., Di Cristina, A., Roberti, M., Pizzirani, D., Meli, M., Dusonchet, L., Gebbia, N., Abbadessa, V., Crosta, L., et al. (2005). Pterostilbene and 3'-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells. Int J Biochem Cell Biol 37, 1709-1726.
Wedel, S., Hudak, L., Seibel, J. M., Makarevic, J., Juengel, E., Tsaur, I., Wiesner, C., Haferkamp, A., and Blaheta, R. A. (2011). Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells. Clin Exp Metastasis 28, 479-491.
Wierzbicka-Patynowski, I., and Schwarzbauer, J. E. (2003). The ins and outs of fibronectin matrix assembly. J Cell Sci 116, 3269-3276.
Wyckoff, J. B., Jones, J. G., Condeelis, J. S., and Segall, J. E. (2000). A critical step in
metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60, 2504-2511.
Zhang, G., Brewster, A., Guan, B., Fan, Z., Brown, P. H., and Xu, X. C. (2011).
Tumor-suppressor activity of RRIG1 in breast cancer. BMC Cancer 11, 32.
Zhang, L., Zhou, W., Velculescu, V. E., Kern, S. E., Hruban, R. H., Hamilton, S. R., Vogelstein, B., and Kinzler, K. W. (1997). Gene expression profiles in normal and cancer
cells. Science 276, 1268-1272.
Zhou, J., Chen, Y., Lang, J. Y., Lu, J. J., and Ding, J. (2008). Salvicine inactivates beta 1 integrin and inhibits adhesion of MDA-MB-435 cells to fibronectin via reactive oxygen species signaling. Mol Cancer Res 6, 194-204.
Zuo, J. H., Zhu, W., Li, M. Y., Li, X. H., Yi, H., Zeng, G. Q., Wan, X. X., He, Q. Y., Li, J. H., Qu, J. Q., et al. (2011). Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin. J Cell Biochem.