| 研究生: |
王麒隆 Wang, Chi-Lung |
|---|---|
| 論文名稱: |
探討IL-8在化療後調控大腸直腸癌轉移中的角色 Investigating the role of IL-8 in regulating metastasis of colorectal cancer after chemotherapy |
| 指導教授: |
陳炳焜
Chen, Ben-Kuen |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 藥理學研究所 Department of Pharmacology |
| 論文出版年: | 2025 |
| 畢業學年度: | 113 |
| 語文別: | 英文 |
| 論文頁數: | 93 |
| 中文關鍵詞: | IL-8 、結直腸癌 、抗藥性 、轉移 、血管新生 |
| 外文關鍵詞: | IL-8, colorectal cancer, chemoresistance, metastasis, angiogenesis |
| 相關次數: | 點閱:8 下載:0 |
| 分享至: |
| 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 |
結直腸癌(colorectal cancer, CRC)是全球第三常見的癌症,同時也是導致癌症相關死亡的主要原因之一。儘管治療方式已有進步,轉移與藥物抗性仍為臨床上的重大挑戰。奧沙利鉑(Oxaliplatin, OXA)為治療結直腸癌的標準化療藥物,但許多患者在接受治療後仍會產生抗藥性,導致其療效受限。為探討化療後促進轉移的機制,我們建立了一套模擬化療後殘存腫瘤細胞的化療存活(OXA-S)細胞模型。OXA-S 細胞表現出生長緩慢、具藥物抗性、活性氧(ROS)上升,以及與上皮-間質轉化(EMT)和癌幹性(cancer stemness)相關基因的表現增加。在多個潛在候選的基因中,IL-8 表現顯著上調,並被挑選作為後續研究之分子。功能性實驗結果顯示,由OXA-S細胞所分泌之IL-8 可促進 EMT 特徵、提升細胞侵襲性、增加內皮通透性並促進血管新生;上述效應可透過 IL-8 基因沉默或中和抗體阻斷。體內實驗中,抑制 IL-8 能夠有效抑制肺部轉移研究結果指出,IL-8 可能是抑制化療後結直腸癌細胞轉移的潛在標的。
Colorectal cancer (CRC) is commonly diagnosed cancer as the third priority in the world and a leading cause of cancer-related death. Despite advances in treatment, metastasis and drug resistance remain major clinical challenges. Oxaliplatin (OXA) is a standard chemotherapeutic agent for CRC, but many patients eventually developed resistance after treatment, limiting the therapeutic efficacy. To investigate the mechanisms driving post-chemotherapy metastasis, we established a chemotherapy-surviving (OXA-S) cell model that mimics residual colorectal tumor cells. OXA-S cells exhibited slow proliferation, drug resistance, elevated ROS level, and increased expression of genes associated with epithelial–mesenchymal transition (EMT) and cancer stemness. Among the potential candidates, IL-8 was markedly upregulated and selected for further characterization. Functional assays revealed that OXA-S-secreted IL-8 promotes EMT features, enhances cell invasiveness, increases endothelial permeability, and stimulates angiogenesis. These effects were reversed by IL-8 knockdown or neutralizing antibody. In vivo, IL-8 depletion suppressed lung metastasis. Our findings suggest IL-8 as a promising target to inhibit metastasis following chemotherapy in CRC.
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA: A Cancer Journal for Clinicians. 2024;74(1):12-49.
2. Johnson CM, Wei C, Ensor JE, Smolenski DJ, Amos CI, Levin B, et al. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control. 2013;24(6):1207-22.
3. Sandler RS. EPIDEMIOLOGY AND RISK FACTORS FOR COLORECTAL CANCER. Gastroenterology Clinics. 1996;25(4):717-35.
4. Amersi F, Agustin M, Ko CY. Colorectal cancer: epidemiology, risk factors, and health services. Clinics in Colon and Rectal Surgery. 2005;18(3):133-40.
5. Li Q, Geng S, Luo H, Wang W, Mo Y-Q, Luo Q, et al. Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy. Signal Transduction and Targeted Therapy. 2024;9(1):266.
6. Obuch JC, Pigott CM, Ahnen DJ. Sessile serrated polyps: detection, eradication, and prevention of the evil twin. Current Treatment Options in Gastroenterology. 2015;13(1):156-70.
7. Crockett SD. Sessile Serrated Polyps and Colorectal Cancer. JAMA. 2017;317(9):975-6.
8. Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010;138(6):2059-72.
9. Boland CR, Goel A. Microsatellite Instability in Colorectal Cancer. Gastroenterology. 2010;138(6):2073-87.e3.
10. Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR. The CpG island methylator phenotype (CIMP) in colorectal cancer. Gastroenterology and Hepatology from Bed to Bench. 2013;6(3):120-8.
11. Boutin AT, Liao WT, Wang M, Hwang SS, Karpinets TV, Cheung H, et al. Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes and Development. 2017;31(4):370-82.
12. Nguyen HT, Duong HQ. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy (Review). Oncology Letters. 2018;16(1):9-18.
13. Zlobec I, Lugli A. Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer: Tumor budding as oncotarget. Oncotarget. 2010;1(7).
14. Sánchez-Tilló E, Pedrosa L, Vila I, Chen Y, Győrffy B, Sánchez-Moral L, et al. The EMT factor ZEB1 paradoxically inhibits EMT in BRAF-mutant carcinomas. JCI Insight. 2023;8(20).
15. Takeda M, Yoshida S, Inoue T, Sekido Y, Hata T, Hamabe A, et al. The Role of KRAS Mutations in Colorectal Cancer: Biological Insights, Clinical Implications, and Future Therapeutic Perspectives. Cancers. 2025;17(3).
16. Maffeis V, Nicolè L, Cappellesso R. RAS, Cellular Plasticity, and Tumor Budding in Colorectal Cancer. Frontiers in Oncology. 2019;9:1255.
17. Vu T, Datta PK. Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis. Cancers. 2017;9(12).
18. Dehal AN, Graff-Baker AN, Vuong B, Nelson D, Chang S-C, Lee DY, et al. Correlation Between Clinical and Pathologic Staging in Colon Cancer: Implications for Neoadjuvant Treatment. Journal of Gastrointestinal Surgery. 2018;22(10):1764-71.
19. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.
20. Cheong CK, Nistala KRY, Ng CH, Syn N, Chang HSY, Sundar R, et al. Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review. Journal of Gastrointestinal Oncology. 2020;11(5):847-57.
21. Kumar A, Gautam V, Sandhu A, Rawat K, Sharma A, Saha L. Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review. World Journal of Gastrointestinal Surgery. 2023;15(4):495-519.
22. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Version 2025. Plymouth Meeting (PA): NCCN; 2025. Available from: https://www.nccn.org
23. Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, et al. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). British Journal of Cancer. 2006;94(6):798-805.
24. Neugut AI, Lin A, Raab GT, Hillyer GC, Keller D, O'Neil DS, et al. FOLFOX and FOLFIRI Use in Stage IV Colon Cancer: Analysis of SEER-Medicare Data. Clinical Colorectal Cancer. 2019;18(2):133-40.
25. Huy TL, Bui MH, Dinh TC, Xuyen HTH. Efficacy and Toxicity of Folfoxiri for Patients with Metastatic Colorectal Cancer. Open Access Macedonian Journal of Medical Sciences. 2019;7(24):4244-9.
26. Morris VK, Kennedy EB, Baxter NN, Benson AB, Cercek A, Cho M, et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. Journal of Clinical Oncology. 2022;41(3):678-700.
27. Gong J, Cho M, Fakih M. RAS and BRAF in metastatic colorectal cancer management. Journal of Gastrointestinal Oncology. 2016;7(5):687-704.
28. Kopetz S, Yoshino T, Van Cutsem E, Eng C, Kim TW, Wasan HS, et al. Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nature Medicine. 2025;31(3):901-8.
29. Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nature Reviews Gastroenterology & Hepatology. 2019;16(6):361-75.
30. Zhao B, Wang L, Qiu H, Zhang M, Sun L, Peng P, et al. Mechanisms of resistance to anti-EGFR therapy in colorectal cancer. Oncotarget. 2017;8(3):3980-4000.
31. US Food and Drug Administration. FDA approves sotorasib plus panitumumab for KRAS G12C–mutated colorectal cancer. Silver Spring (MD): FDA; 2024 [updated 2025 Jun 15; cited 2025 Aug 25]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer
32. Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. New England Journal of Medicine. 2023;389(23):2125-39.
33. Meng M, Zhong K, Jiang T, Liu Z, Kwan HY, Su T. The current understanding on the impact of KRAS on colorectal cancer. Biomedicine and Pharmacotherapy. 2021;140:111717.
34. She Q-B, Solit DB, Ye Q, O’Reilly KE, Lobo J, Rosen N. The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells. Cancer Cell. 2005;8(4):287-97.
35. Soleimani A, Rahmani F, Saeedi N, Ghaffarian R, Khazaei M, Ferns GA, et al. The potential role of regulatory microRNAs of RAS/MAPK signaling pathway in the pathogenesis of colorectal cancer. Journal of Cellular Biochemistry. 2019;120(12):19245-53.
36. Tao S, Wang S, Moghaddam SJ, Ooi A, Chapman E, Wong PK, et al. Oncogenic KRAS confers chemoresistance by upregulating NRF2. Cancer Research. 2014;74(24):7430-41.
37. Kalimutho M, Bain AL, Mukherjee B, Nag P, Nanayakkara DM, Harten SK, et al. Enhanced dependency of KRAS-mutant colorectal cancer cells on RAD51-dependent homologous recombination repair identified from genetic interactions in Saccharomyces cerevisiae. Molecular Oncology. 2017;11(5):470-90.
38. Shi R, Cheng Y, Wang J, Song N, Chen Y, Teng Z, et al. Genetic feature diversity of KRAS-mutated colorectal cancer and the negative association of DNA mismatch repair deficiency relevant mutational signatures with prognosis. Genes & Diseases. 2025;12(1):101245.
39. Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K. Essential involvement of interleukin-8 (IL-8) in acute inflammation. Journal of Leukocyte Biology. 1994;56(5):559-64.
40. Matsushima K, Yang D, Oppenheim JJ. Interleukin-8: An evolving chemokine. Cytokine. 2022;153:155828.
41. Shao Y, Lan Y, Chai X, Gao S, Zheng J, Huang R, et al. CXCL8 induces M2 macrophage polarization and inhibits CD8+ T cell infiltration to generate an immunosuppressive microenvironment in colorectal cancer. The FASEB Journal. 2023;37(10):e23173.
42. Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis. International Journal of Inflammation. 2011;2011:908468.
43. Grimm MC, Elsbury SK, Pavli P, Doe WF. Interleukin 8: cells of origin in inflammatory bowel disease. Gut. 1996;38(1):90-8.
44. Vlahopoulos S, Boldogh I, Casola A, Brasier AR. Nuclear Factor-κB–Dependent Induction of Interleukin-8 Gene Expression by Tumor Necrosis Factor α: Evidence for an Antioxidant Sensitive Activating Pathway Distinct From Nuclear Translocation. Blood. 1999;94(6):1878-89.
45. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nature Reviews Cancer. 2009;9(11):798-809.
46. Hoffmann E, Dittrich-Breiholz O, Holtmann H, Kracht M. Multiple control of interleukin-8 gene expression. Journal of Leukocyte Biology. 2002;72(5):847-55.
47. Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine and Growth Factor Reviews. 2010;21(1):11-9.
48. Chen Y, Shi M, Yu GZ, Qin XR, Jin G, Chen P, et al. Interleukin-8, a promising predictor for prognosis of pancreatic cancer. World Journal of Gastroenterology. 2012;18(10):1123-9.
49. Belluomini L, Cesta Incani U, Smimmo A, Avancini A, Sposito M, Insolda J, et al. Prognostic impact of Interleukin-8 levels in lung cancer: A meta-analysis and a bioinformatic validation. Lung Cancer. 2024;194:107893.
50. Bazzichetto C, Milella M, Zampiva I, Simionato F, Amoreo CA, Buglioni S, et al. Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker. Biomedicines. 2022;10(10).
51. Rizzo M, Varnier L, Pezzicoli G, Pirovano M, Cosmai L, Porta C. IL-8 and its role as a potential biomarker of resistance to anti-angiogenic agents and immune checkpoint inhibitors in metastatic renal cell carcinoma. Frontiers in Oncology. 2022;Volume 12 - 2022.
52. Rubie C, Frick VO, Pfeil S, Wagner M, Kollmar O, Kopp B, et al. Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer. World Journal of Gastroenterology. 2007;13(37):4996-5002.
53. Ning Y, Lenz HJ. Targeting IL-8 in colorectal cancer. Expert Opinion on Therapeutic Targets. 2012;16(5):491-7.
54. Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology. 2014;15(3):178-96.
55. Conciatori F, Bazzichetto C, Falcone I, Ferretti G, Cognetti F, Milella M, et al. Colorectal cancer stem cells properties and features: evidence of interleukin-8 involvement. Cancer Drug Resistance. 2019;2(4):968-79.
56. Choi HS, Kim JH, Kim SL, Lee DS. Disruption of the NF-κB/IL-8 Signaling Axis by Sulconazole Inhibits Human Breast Cancer Stem Cell Formation. Cells. 2019;8(9).
57. Findlay VJ, Wang C, Watson DK, Camp ER. Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: insights from cancer biology with therapeutic implications for colorectal cancer. Cancer Gene Therapy. 2014;21(5):181-7.
58. Barriere G, Fici P, Gallerani G, Fabbri F, Zoli W, Rigaud M. Circulating tumor cells and epithelial, mesenchymal and stemness markers: characterization of cell subpopulations. Annals of Translational Medicine. 2014;2(11):109.
59. Liu T, Ma Q, Zhang Y, Wang X, Xu K, Yan K, et al. Self-seeding circulating tumor cells promote the proliferation and metastasis of human osteosarcoma by upregulating interleukin-8. Cell Death & Disease. 2019;10(8):575.
60. Fousek K, Horn LA, Palena C. Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression. Pharmacology and Therapeutics. 2021;219:107692.
61. Lee YS, Choi I, Ning Y, Kim NY, Khatchadourian V, Yang D, et al. Interleukin-8 and its receptor CXCR2 in the tumour microenvironment promote colon cancer growth, progression and metastasis. British Journal of Cancer. 2012;106(11):1833-41.
62. Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clinical Cancer Research. 2008;14(21):6735-41.
63. Milosevic V, Kopecka J, Salaroglio IC, Libener R, Napoli F, Izzo S, et al. Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5. International Journal of Cancer. 2020;146(1):192-207.
64. Palena C, Hamilton DH, Fernando RI. Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncology. 2012;8(6):713-22.
65. Fernando RI, Castillo MD, Litzinger M, Hamilton DH, Palena C. IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Research. 2011;71(15):5296-306.
66. Cui G, Yuan A, Goll R, Vonen B, Florholmen J. Dynamic changes of interleukin-8 network along the colorectal adenoma-carcinoma sequence. Cancer Immunology, Immunotherapy. 2009;58(11):1897-905.
67. Li A, Dubey S, Varney ML, Dave BJ, Singh RK. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. Journal of Immunology. 2003;170(6):3369-76.
68. Mizukami Y, Jo WS, Duerr EM, Gala M, Li J, Zhang X, et al. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nature Medicine. 2005;11(9):992-7.
69. Yu H, Huang X, Ma Y, Gao M, Wang O, Gao T, et al. Interleukin-8 regulates endothelial permeability by down-regulation of tight junction but not dependent on integrins induced focal adhesions. International Journal of Biological Sciences. 2013;9(9):966-79.
70. Sanmamed MF, Carranza-Rua O, Alfaro C, Oñate C, Martín-Algarra S, Perez G, et al. Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins. Clinical Cancer Research. 2014;20(22):5697-707.
71. Hasan T, Caragher SP, Shireman JM, Park CH, Atashi F, Baisiwala S, et al. Interleukin-8/CXCR2 signaling regulates therapy-induced plasticity and enhances tumorigenicity in glioblastoma. Cell Death & Disease. 2019;10(4):292.
72. He J, Qiu Z, Fan J, Xie X, Sheng Q, Sui X. Drug tolerant persister cell plasticity in cancer: a revolutionary strategy for more effective anticancer therapies. Signal Transduction and Targeted Therapy. 2024;9(1):209.
73. Rehman SK, Haynes J, Collignon E, Brown KR, Wang Y, Nixon AML, et al. Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy. Cell. 2021;184(1):226-42.e21.
74. Chou Y-T, Allegakoen P, Bivona TG. Targeting Minimal Residual Disease. Annual Review of Cancer Biology. 2025;9(Volume 9, 2025):205-23.
75. Dhanyamraju PK, Schell TD, Amin S, Robertson GP. Drug-Tolerant Persister Cells in Cancer Therapy Resistance. Cancer Research. 2022;82(14):2503-14.
76. Liang X-W, Liu B-, Chen J-C, Cao Z, Chu F-r, Lin X, et al. Characteristics and molecular mechanism of drug-tolerant cells in cancer: a review. Frontiers in Oncology. 2023;Volume 13 - 2023.
77. Raha D, Wilson TR, Peng J, Peterson D, Yue P, Evangelista M, et al. The Cancer Stem Cell Marker Aldehyde Dehydrogenase Is Required to Maintain a Drug-Tolerant Tumor Cell Subpopulation. Cancer Research. 2014;74(13):3579-90.
78. Li M, Nishimura T, Takeuchi Y, Hongu T, Wang Y, Shiokawa D, et al. FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters. The Journal of Clinical Investigation. 2023;133(22).
79. Pu Y, Li L, Peng H, Liu L, Heymann D, Robert C, et al. Drug-tolerant persister cells in cancer: the cutting edges and future directions. Nature Reviews: Clinical Oncology. 2023;20(11):799-813.
80. Böpple K, Oren Y, Henry WS, Dong M, Weller S, Thiel J, et al. ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC. Cell Death & Disease. 2024;15(4):290.
81. Zhang Z, Tan Y, Huang C, Wei X. Redox signaling in drug-tolerant persister cells as an emerging therapeutic target. eBioMedicine. 2023;89.
82. Leonce C, Saintigny P, Ortiz-Cuaran S. Cell-Intrinsic Mechanisms of Drug Tolerance to Systemic Therapies in Cancer. Molecular Cancer Research. 2022;20(1):11-29.
83. Russo M, Chen M, Mariella E, Peng H, Rehman SK, Sancho E, et al. Cancer drug-tolerant persister cells: from biological questions to clinical opportunities. Nature Reviews Cancer. 2024;24(10):694-717.
84. Pérez-González A, Bévant K, Blanpain C. Cancer cell plasticity during tumor progression, metastasis and response to therapy. Nature cancer. 2023;4(8):1063-82.
85. Wajapeyee N, Gupta R. Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies. Cancer Research. 2021;81(22):5589-95.
86. Carpentier G, Berndt S, Ferratge S, Rasband W, Cuendet M, Uzan G, et al. Angiogenesis Analyzer for ImageJ — A comparative morphometric analysis of “Endothelial Tube Formation Assay” and “Fibrin Bead Assay”. Scientific Reports. 2020;10(1):11568.
87. Punzi S, Cittaro D, Gatti G, Crupi G, Botrugno OA, Cartalemi AA, et al. Early tolerance and late persistence as alternative drug responses in cancer. Nature Communications. 2025;16(1):1291.
88. Chen L, Fan J, Chen H, Meng Z, Chen Z, Wang P, et al. The IL-8/CXCR1 axis is associated with cancer stem cell-like properties and correlates with clinical prognosis in human pancreatic cancer cases. Scientific Reports. 2014;4(1):5911.
89. Nakano K, Oki E, Yamazaki M, Suzuki M, Kawai S, Fujita T, et al. Colorectal cancer cell line-derived organoid model with stem cell properties captures the regrowing state of residual cancer cells after neoadjuvant chemotherapy. Cell Death Discovery. 2025;11(1):282.
90. Shen S, Vagner S, Robert C. Persistent Cancer Cells: The Deadly Survivors. Cell. 2020;183(4):860-74.
91. Jácome AA, Johnson B. Minimal Residual Disease in Colorectal Cancer: Are We Finding the Needle in a Haystack? Cells. 2023;12(7).
92. Colucci M, Sarill M, Maddalena M, Valdata A, Troiani M, Massarotti M, et al. Senescence in cancer. Cancer Cell. 2025;43(7):1204-26.
93. O’Sullivan EA, Wallis R, Mossa F, Bishop CL. The paradox of senescent-marker positive cancer cells: challenges and opportunities. npj Aging. 2024;10(1):41.
94. Truskowski K, Amend SR, Pienta KJ. Dormant cancer cells: programmed quiescence, senescence, or both? Cancer and Metastasis Reviews. 2023;42(1):37-47.
95. Pluquet O, Abbadie C, Coqueret O. Connecting cancer relapse with senescence. Cancer Letters. 2019;463:50-8.
96. Jin P, Duan X, Li L, Zhou P, Zou CG, Xie K. Cellular senescence in cancer: molecular mechanisms and therapeutic targets. MedComm. 2024;5(5):e542.
97. Aguirre-Portolés C, Feliu J, Reglero G, Ramírez de Molina A. ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone. Molecular Oncology. 2018;12(10):1735-52.
98. Mordzińska-Rak A, Verdeil G, Hamon Y, Błaszczak E, Trombik T. Dysregulation of cholesterol homeostasis in cancer pathogenesis. Cellular and Molecular Life Sciences. 2025;82(1):168.
99. Candeil L, Gourdier I, Peyron D, Vezzio N, Copois V, Bibeau F, et al. ABCG2 overexpression in colon cancer cells resistant to SN38 and in irinotecan-treated metastases. International Journal of Cancer. 2004;109(6):848-54.
100. Farrokhnazar E, Moghbelinejad S, Najafipour R, Teimoori-Toolabi L. MiR-3664-3p through suppressing ABCG2, CYP3A4, MCL1, and MLH1 increases the sensitivity of colorectal cancer cells to irinotecan. Heliyon. 2025;11(3):e41933.
101. Chen R, Yu Y, Liu R, Chen Q. Targeting breast cancer resistance protein (BCRP/ABCG2) in cancer. Translational Cancer Research. 2024;13(11):6550-64.
102. Vona R, Iessi E, Matarrese P. Role of Cholesterol and Lipid Rafts in Cancer Signaling: A Promising Therapeutic Opportunity? Frontiers in Cell and Developmental Biology. 2021;Volume 9 - 2021.
103. He X, Wang J, Wei W, Shi M, Xin B, Zhang T, et al. Hypoxia regulates ABCG2 activity through the activivation of ERK1/2/HIF-1α and contributes to chemoresistance in pancreatic cancer cells. Cancer Biology & Therapy. 2016;17(2):188-98.
104. Teijeira A, Garasa S, Ochoa MC, Villalba M, Olivera I, Cirella A, et al. IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy. Clinical Cancer Research. 2021;27(9):2383-93.
105. Yang L, Liu L, Zhang R, Hong J, Wang Y, Wang J, et al. IL-8 mediates a positive loop connecting increased neutrophil extracellular traps (NETs) and colorectal cancer liver metastasis. Journal of Cancer. 2020;11(15):4384-96.
106. He B, Ganss R. Modulation of the Vascular-Immune Environment in Metastatic Cancer. Cancers. 2021;13(4).
107. David JM, Dominguez C, Hamilton DH, Palena C. The IL-8/IL-8R Axis: A Double Agent in Tumor Immune Resistance. Vaccines. 2016;4(3).
108. Petreaca ML, Yao M, Liu Y, Defea K, Martins-Green M. Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8/CXCL8) is required for IL-8/CXCL8-induced endothelial permeability. Molecular Biology of the Cell. 2007;18(12):5014-23.
109. Gavard J, Gutkind JS. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nature Cell Biology. 2006;8(11):1223-34.
110. Vestweber D. VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28(2):223-32.
111. Hadpech S, Peerapen P, Thongboonkerd V. The upregulation of lamin A/C as a compensatory mechanism during tight junction disruption in renal tubular cells mediated by calcium oxalate crystals. Current Research in Toxicology. 2024;6:100145.
112. Moztarzadeh S, Radeva MY, Sepic S, Schuster K, Hamad I, Waschke J, et al. Lack of adducin impairs the stability of endothelial adherens and tight junctions and may be required for cAMP-Rac1-mediated endothelial barrier stabilization. Scientific Reports. 2022;12(1):14940.
113. 李念綺, Li N-C. 探討抗發炎於化療後存活之大腸直腸癌細胞轉移的影響 Investigating the effect of anti-inflammation on the metastasis of chemo-surviving colorectal cancer cells / 李念綺(Nien-Chi Li)撰: 國立成功大學藥理學研究所; 2022.
校內:2030-08-29公開