Yonsei Medical Journal

Yonsei Univ College Medicine (연세대학교의과대학)
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Heat Shock Factor 1 Predicts Poor Prognosis of Gastric Cancer

  • Kim, Seok-Jun (Department of Biomedical Science, College of Natural Science, Chosun University) ;
  • Lee, Seok-Cheol (Department of Biomedical Science, College of Natural Science, Chosun University) ;
  • Kang, Hyun-Gu (Department of Biomedical Science, College of Natural Science, Chosun University) ;
  • Gim, Jungsoo (Department of Biomedical Science, College of Natural Science, Chosun University) ;
  • Lee, Kyung-Hwa (Department of Pathology, Chonnam National University Medical School) ;
  • Lee, Seung-Hyun (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine) ;
  • Chun, Kyung-Hee (Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine)
  • Received : 2018.06.15
  • Accepted : 2018.08.31
  • Published : 2018.11.01
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Abstract

Purpose: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. Materials and Methods: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. Results: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). Conclusion: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

Keywords

Acknowledgement

Supported by : NRF

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115-32. https://doi.org/10.3322/caac.21338
  3. Rahman R, Asombang AW, Ibdah JA. Characteristics of gastric cancer in Asia. World J Gastroenterol 2014;20:4483-90. https://doi.org/10.3748/wjg.v20.i16.4483
  4. Link A, Kupcinskas J. MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer: current insights and future perspectives. World J Gastroenterol 2018;24:3313-29. https://doi.org/10.3748/wjg.v24.i30.3313
  5. Ji X, Yan Y, Bu ZD, Li ZY, Wu AW, Zhang LH, et al. The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival. BMC Cancer 2017;17:345. https://doi.org/10.1186/s12885-017-3343-0
  6. Yuan DD, Zhu ZX, Zhang X, Liu J. Targeted therapy for gastric cancer: current status and future directions (Review). Oncol Rep 2016;35:1245-54. https://doi.org/10.3892/or.2015.4528
  7. Kanat O, O'Neil B, Shahda S. Targeted therapy for advanced gastric cancer: a review of current status and future prospects. World J Gastrointest Oncol 2015;7:401-10. https://doi.org/10.4251/wjgo.v7.i12.401
  8. Lin Y, Wu Z, Guo W, Li J. Gene mutations in gastric cancer: a review of recent next-generation sequencing studies. Tumour Biol 2015;36:7385-94. https://doi.org/10.1007/s13277-015-4002-1
  9. Calderwood SK. HSF1, a versatile factor in tumorogenesis. Curr Mol Med 2012;12:1102-7. https://doi.org/10.2174/156652412803306675
  10. Tomanek L, Somero GN. Interspecific- and acclimation-induced variation in levels of heat-shock proteins 70 (hsp70) and 90 (hsp90) and heat-shock transcription factor-1 (HSF1) in congeneric marine snails (genus Tegula): implications for regulation of hsp gene expression. J Exp Biol 2002;205(Pt 5):677-85.
  11. Neueder A, Gipson TA, Batterton S, Lazell HJ, Farshim PP, Paganetti P, et al. HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models. Sci Rep 2017;7:12556. https://doi.org/10.1038/s41598-017-12897-0
  12. Zhang Y, Huang L, Zhang J, Moskophidis D, Mivechi NF. Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue-specific regulation for stress-inducible Hsp molecular chaperones. J Cell Biochem 2002;86:376-93. https://doi.org/10.1002/jcb.10232
  13. Gomez AV, Cordova G, Munita R, Parada GE, Barrios AP, Cancino GI, et al. Characterizing HSF1 binding and post-translational modifications of hsp70 promoter in cultured cortical neurons: implications in the heat-shock response. PLoS One 2015;10:e0129329. https://doi.org/10.1371/journal.pone.0129329
  14. Verma P, Pfister JA, Mallick S, D'Mello SR. HSF1 protects neurons through a novel trimerization- and HSP-independent mechanism. J Neurosci 2014;34:1599-612. https://doi.org/10.1523/JNEUROSCI.3039-13.2014
  15. Santagata S, Hu R, Lin NU, Mendillo ML, Collins LC, Hankinson SE, et al. High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. Proc Natl Acad Sci U S A 2011;108:18378-83. https://doi.org/10.1073/pnas.1115031108
  16. Kang MJ, Yun HH, Lee JH. KRIBB11 accelerates Mcl-1 degradation through an HSF1-independent, Mule-dependent pathway in A549 non-small cell lung cancer cells. Biochem Biophys Res Commun 2017;492:304-9. https://doi.org/10.1016/j.bbrc.2017.08.118
  17. Chen K, Qian W, Li J, Jiang Z, Cheng L, Yan B, et al. Loss of AMPK activation promotes the invasion and metastasis of pancreatic cancer through an HSF1-dependent pathway. Mol Oncol 2017;11:1475-92. https://doi.org/10.1002/1878-0261.12116
  18. Wan T, Shao J, Hu B, Liu G, Luo P, Zhou Y. Prognostic role of HSF1 overexpression in solid tumors: a pooled analysis of 3,159 patients. Onco Targets Ther 2018;11:383-93. https://doi.org/10.2147/OTT.S153682
  19. La SH, Kim SJ, Kang HG, Lee HW, Chun KH. Ablation of human telomerase reverse transcriptase (hTERT) induces cellular senescence in gastric cancer through a galectin-3 dependent mechanism. Oncotarget 2016;7:57117-30.
  20. Kim SJ, Wang YG, Lee HW, Kang HG, La SH, Choi IJ, et al. Up-regulation of neogenin-1 increases cell proliferation and motility in gastric cancer. Oncotarget 2014;5:3386-98.
  21. Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget 2016;7:49322-33.
  22. Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 1998;94:471-80. https://doi.org/10.1016/S0092-8674(00)81588-3
  23. Dai C. The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis. Philos Trans R Soc Lond B Biol Sci 2018;373:20160525. https://doi.org/10.1098/rstb.2016.0525
  24. Wang RE. Targeting heat shock proteins 70/90 and proteasome for cancer therapy. Curr Med Chem 2011;18:4250-64. https://doi.org/10.2174/092986711797189574
  25. Jego G, Hazoume A, Seigneuric R, Garrido C. Targeting heat shock proteins in cancer. Cancer Lett 2013;332:275-85. https://doi.org/10.1016/j.canlet.2010.10.014
  26. Li Q, Feldman RA, Radhakrishnan VM, Carey S, Martinez JD. Hsf1 is required for the nuclear translocation of p53 tumor suppressor. Neoplasia 2008;10:1138-45. https://doi.org/10.1593/neo.08430
  27. Sharma A, Meena AS, Bhat MK. Hyperthermia-associated carboplatin resistance: differential role of p53, HSF1 and Hsp70 in hepatoma cells. Cancer Sci 2010;101:1186-93. https://doi.org/10.1111/j.1349-7006.2010.01516.x
  28. Cigliano A, Wang C, Pilo MG, Szydlowska M, Brozzetti S, Latte G, et al. Inhibition of HSF1 suppresses the growth of hepatocarcinoma cell lines in vitro and AKT-driven hepatocarcinogenesis in mice. Oncotarget 2017;8:54149-59.
  29. Gokmen-Polar Y, Badve S. Upregulation of HSF1 in estrogen receptor positive breast cancer. Oncotarget 2016;7:84239-45.
  30. Rossi A, Ciafre S, Balsamo M, Pierimarchi P, Santoro MG. Targeting the heat shock factor 1 by RNA interference: a potent tool to enhance hyperthermochemotherapy efficacy in cervical cancer. Cancer Res 2006;66:7678-85. https://doi.org/10.1158/0008-5472.CAN-05-4282
  31. Cen H, Zheng S, Fang YM, Tang XP, Dong Q. Induction of HSF1 expression is associated with sporadic colorectal cancer. World J Gastroenterol 2004;10:3122-6. https://doi.org/10.3748/wjg.v10.i21.3122

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