A synergistic interaction between transcription factors nuclear factor-κB and signal transducers and activators of transcription 3 promotes gastric cancer cell migration and invasion

详细信息    查看全文

• 作者：Jiyeon Yoon (1)
  Sung Jin Cho (1)
  Young San Ko (1)
  Jinju Park (2)
  Dong Hoon Shin (1)
  In Chan Hwang (1)
  Sang Yeun Han (3)
  Seon Young Nam (4)
  Min A Kim (5)
  Mee Soo Chang (5)
  Hye Seung Lee (6)
  Woo Ho Kim (2) (5)
  Byung Lan Lee (1) (2) (7)
  
• 刊名：BMC Gastroenterology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：496KB
• 参考文献：1. Ma L, Weinberg RA: Micromanagers of malignancy: role of microRNAs in regulating metastasis. / Trends Genet 2008, 24:448-56. CrossRef
  2. Hartgrink HH, Jansen EP, Van Grieken NC, van de Velde CJ: Gastric cancer. / Lancet 2009, 374:477-90. CrossRef
  3. Han SS, Yun H, Son DJ, Tompkins VS, Peng L, Chung ST, Kim JS, Park ES, Janz S: NF-κB/STAT3/PI3K signaling crosstalk in iMyc E mu B lymphoma. / Mol Cancer 2010, 9:97-13. CrossRef
  4. Pahl HL: Activators and target genes of Rel/NF-κB transcription factors. / Oncogene 1999, 18:6853-866. CrossRef
  5. Gilmore TD: The Rel/NF-κB signal transduction pathway: introduction. / Oncogene 1999, 18:6842-844. CrossRef
  6. Kuai WX, Wang Q, Yang XZ, Zhao Y, Yu R, Tang XJ: Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity of human gastric cancer cells. / World J Gastroenterol 2012, 18:979-85. CrossRef
  7. Hong S, Lee C, Kim SJ: Smad7 sensitizes tumor necrosis factor induced apoptosis through the inhibition of antiapoptotic gene expression by suppressing activation of the nuclear factor-κB pathway. / Cancer Res 2007, 67:9577-583. CrossRef
  8. Soutto M, Belkhiri A, Piazuelo MB, Schneider BG, Peng D, Jiang A, Washington MK, Kokoye Y, Crowe SE, Zaika A, Correa P, Peek RM Jr, El-Rifai W: Loss of TFF1 is associated with activation of NF-κB-mediated inflammation and gastric neoplasia in mice and humans. / J Clin Invest 2011, 121:1753-767. CrossRef
  9. Lee KH, Kim JR: Regulation of HGF-mediated cell proliferation and invasion through NF-κB, JunB, and MMP-9 cascades in stomach cancer cells. / Clin Exp Metastasis 2012, 29:263-72. CrossRef
  10. Song EJ, Kang MJ, Kim YS, Kim SM, Lee SE, Kim CH, Kim DJ, Park JH: Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5. / Int J Mol Med 2011, 28:115-19.
  11. Viala J, Chaput C, Boneca IG, Cardona A, Girardin SE, Moran AP, Athman R, Mémet S, Huerre MR, Coyle AJ, DiStefano PS, Sansonetti PJ, Labigne A, Bertin J, Philpott DJ, Ferrero RL: Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. / Nat Immunol 2004, 5:1166-174. CrossRef
  12. Lamb A, Chen LF: The many roads traveled by Helicobacter pylori to NFκB activation. / Gut Microbes 2010, 1:109-13. CrossRef
  13. Feng W, Brown RE, Trung CD, Li W, Wang L, Khoury T, Alrawi S, Yao J, Xia K, Tan D: Morphoproteomic profile of mTOR, Ras/Raf kinase/ERK, and NF-κB pathways in human gastric adenocarcinoma. / Ann Clin Lab Sci 2008, 38:195-09.
  14. Long YM, Ye S, Rong J, Xie WR: Nuclear factor-κB: a marker of chemotherapy for human stage IV gastric carcinoma. / World J Gastroenterol 2008, 14:4739-744. CrossRef
  15. Wu L, Pu Z, Feng J, Li G, Zheng Z, Shen W: The ubiquitin-proteasome pathway and enhanced activity of NF-κB in gastric carcinoma. / J Surg Oncol 2008, 97:439-44. CrossRef
  16. Kang MH, Oh SC, Lee HJ, Kang HN, Kim JL, Kim JS, Yoo YA: Metastatic function of BMP-2 in gastric cancer cells: the role of PI3K/AKT, MAPK, the NF-κB pathway, and MMP-9 expression. / Exp Cell Res 2011, 317:1746-762. CrossRef
  17. Koyama S: Differential expression of intracellular apoptotic signaling molecules in tumor and tumor-infiltrating lymphocytes during development of invasion and/or metastasis of gastric carcinoma. / Dig Dis Sci 2003, 48:2290-300. CrossRef
  18. Mao Z, Ma X, Rong Y, Cui L, Wang X, Wu W, Zhang J, Jin D: Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E-cadherin via the NF-κB pathway. / Cancer Sci 2011, 102:104-10. CrossRef
  19. Bhave SL, Teknos TN, Pan Q: Molecular parameters of head and neck cancer metastasis. / Crit Rev Eukaryot Gene Expr 2011, 21:143-53. CrossRef
  20. Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, Dey S, Sung B: Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? / Ann N Y Acad Sci 2009, 1171:59-6. CrossRef
  21. Okamoto W, Okamoto I, Arao T, Yanagihara K, Nishio K, Nakagawa K: Differential roles of STAT3 depending on the mechanism of STAT3 activation in gastric cancer cells. / Br J Cancer 2011, 105:407-12. CrossRef
  22. Chen J, Wang J, Lin L, He L, Wu Y, Zhang L, Yi Z, Chen Y, Pang X, Liu M: Inhibition of STAT3 signaling pathway by nitidine chloride suppressed the angiogenesis and growth of human gastric cancer. / Mol Cancer Ther 2012, 11:277-87. CrossRef
  23. Xiong H, Du W, Wang JL, Wang YC, Tang JT, Hong J, Fang JY: Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. / J Mol Med (Berl) 2012, 90:1037-046. CrossRef
  24. He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, Sieghart W, Peck-Radosavljevic M, Leffert HL, Karin M: Hepatocyte IKKβ/NF-κB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. / Cancer Cell 2010, 17:286-97. CrossRef
  25. Yoon S, Woo SU, Kang JH, Kim K, Shin HJ, Gwak HS, Park S, Chwae YJ: NF-κB and STAT3 cooperatively induce IL6 in starved cancer cells. / Oncogene 2012, 31:3467-481. CrossRef
  26. Wani AA, Jafarnejad SM, Zhou J, Li G: Integrin-linked kinase regulates melanoma angiogenesis by activating NF-κB/interleukin-6 signaling pathway. / Oncogene 2011, 30:2778-788. CrossRef
  27. Lee H, Herrmann A, Deng JH, Kujawski M, Niu G, Li Z, Forman S, Jove R, Pardoll DM, Yu H: Persistently activated Stat3 maintains constitutive NF-κB activity in tumors. / Cancer Cell 2009, 15:283-93. CrossRef
  28. Lee HS, Lee HK, Kim HS, Yang HK, Kim WH: Tumour suppressor gene expression correlates with gastric cancer prognosis. / J Pathol 2003, 200:39-6. CrossRef
  29. Lee HS, Lee HK, Kim HS, Yang HK, Kim YI, Kim WH: MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. / Cancer 2001, 92:1427-434. CrossRef
  30. Chang J, Park K, Bang YJ, Kim WS, Kim D, Kim SJ: Expression of transforming growth factor type II receptor reduces tumorigenicity in human gastric cancer cells. / Cancer Res 1997, 57:2856-859.
  31. Song SH, Jong HS, Choi HH, Inoue H, Tanabe T, Kim NK, Bang YJ: Transcriptional silencing of cyclooxygenase-2 by hyper-methylation of the 5-CpG island in human gastric carcinoma cells. / Cancer Res 2001, 61:4628-635.
  32. Yamada Y, Yoshida T, Hayashi K, Sekiya T, Yokota J, Hirohashi S, Nakatani K, Nakano H, Sugimura T, Terada M: p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases. / Cancer Res 1991, 51:5800-805.
  33. Oh SC, Nam SY, Kwon HC, Kim CM, Seo JS, Seong RH, Jang YJ, Chung YH, Chung HY: Generation of fusion genes carrying drug resistance, green fluorescent protein, and herpes simplex virus thymidine kinase genes in a single cistron. / Mol Cells 2001, 11:192-97.
  34. Nam SY, Jung GA, Hur GC, Chung HY, Kim WH, Seol DW, Lee BL: Upregulation of FLIPS by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers. / Cancer Sci 2003, 94:1066-073. CrossRef
  35. Kim WH, Schnaper HW, Nomizu M, Yamada Y, Kleinman HK: Apoptosis in human fibrosarcoma cells is induced by a multimeric synthetic Tyr-Ile-Gly-Ser-Arg (YIGSR) containing polypeptide from laminin. / Cancer Res 1994, 54:5005-010.
  36. Lewander A, Gao J, Carstensen J, Arbman G, Zhang H, Sun XF: NF-κB p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients. / Int J Colorectal Dis 2012, 27:447-52. CrossRef
  37. Guarino M, Rubino B, Ballabio G: The role of epithelial-mesenchymal transition in cancer pathology. / Pathology 2007, 39:305-18. CrossRef
  38. Wang H, Lafdil F, Kong X, Gao B: Signal transducer and activator of transcription 3 in liver diseases: a novel therapeutic target. / Int J Biol Sci 2011, 7:536-50. CrossRef
  39. Trécul A, Morceau F, Dicato M, Diederich M: Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network. / Genes Nutr 2012, 7:111-25. CrossRef
  40. Yang J, Liao X, Agarwal MK, Barnes L, Auron PE, Stark GR: Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NF-κB. / Genes Dev 2007, 21:1396-408. CrossRef
  41. Kim MA, Lee HS, Lee HE, Kim JH, Yang HK, Kim WH: Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma. / Histopathology 2009, 54:442-51. CrossRef
  42. Katoh M: Epithelial-mesenchymal transition in gastric cancer (Review). / Int J Oncol 2005, 27:1677-683.
  43. Ureshino H, Murakami Y, Watari K, Izumi H, Kawahara A, Kage M, Arao T, Nishio K, Yanagihara K, Kinoshita H, Kuwano M, Ono M: N-myc downstream regulated gene 1 (NDRG1) promotes metastasis of human scirrhous gastric cancer cells through epithelial mesenchymal transition. / PLoS One 2012, 7:e41312. CrossRef
  44. Cho SJ, Park JW, Kang JS, Kim WH, Juhnn YS, Lee JS, Kim YH, Ko YS, Nam SY, Lee BL: Nuclear factor-κB dependency of doxorubicin sensitivity in gastric cancer cells is determined by manganese superoxide dismutase expression. / Cancer Sci 2008, 99:1117-124. CrossRef
  45. Matsuoka T, Yashiro M, Sawada T, Ishikawa T, Ohira M, Hirakawa K, Chung YS: Effect of a matrix metalloproteinase inhibitor on a lymph node metastatic model of gastric cancer cells passaged by orthotopic implantation. / J Exp Clin Cancer Res 2001, 20:213-18.
  46. Chu D, Zhang Z, Li Y, Zheng J, Dong G, Wang W, Ji G: Matrix metalloprotein-9 is associated with disease-free survival and overall survival in patients with gastric cancer. / Int J Cancer 2011, 129:887-95. CrossRef
  47. Liu L, Sun L, Zhao P, Yao L, Jin H, Liang S, Wang Y, Zhang D, Pang Y, Shi Y, Chai N, Zhang H, Zhang H: Hypoxia promotes metastasis in human gastric cancer by up-regulating the 67-kDa laminin receptor. / Cancer Sci 2010, 101:1653-560. CrossRef
  48. Chen Y, Wei X, Guo C, Jin H, Han Z, Han Y, Qiao T, Wu K, Fan D: Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP-1. / Int J Cancer 2011, 129:1586-598. CrossRef
  49. Woodcock J, Griffin JP, Behrman RE: Development of novel combination therapies. / N Engl J Med 2011, 364:985-87. CrossRef
  50. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/13/29/prepub
  
• 作者单位：Jiyeon Yoon (1)
  Sung Jin Cho (1)
  Young San Ko (1)
  Jinju Park (2)
  Dong Hoon Shin (1)
  In Chan Hwang (1)
  Sang Yeun Han (3)
  Seon Young Nam (4)
  Min A Kim (5)
  Mee Soo Chang (5)
  Hye Seung Lee (6)
  Woo Ho Kim (2) (5)
  Byung Lan Lee (1) (2) (7)
  
  1. Department of Anatomy, Seoul National University College of Medicine, Seoul, 110-799, South Korea
  2. Cancer Research Institute, Department of Tumor Biology, Seoul National University College of Medicine, Seoul, 110-799, South Korea
  3. Department of Economics, Cornell University, Ithaca, NY, 14853, USA
  4. Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Ltd, Seoul, 132-703, South Korea
  5. Department of Pathology, Seoul National University College of Medicine, Seoul, 110-799, South Korea
  6. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, 463-707, South Korea
  7. Ischemic/Hypoxic Disease Institute Medical Research Center, Seoul National University College of Medicine, Seoul, 110-799, South Korea
  

文摘

Background The transcription factor nuclear factor-κB (NF-κB) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-κB and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells. Methods Immunohistochemistry for NF-κB p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-κB inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-κB repressor mutant of IκBα, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. Results NF-κB and STAT3 were constitutively activated and were positively correlated (P--.038) in gastric cancer tissue specimens. In cell culture experiments, NF-κB inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-κB activation. Moreover, both NF-κB inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-κB activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P--.001 and P--.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. Conclusion NF-κB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-κB and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.