Tumor Biology

, Volume 37, Issue 7, pp 9849–9854 | Cite as

The tumor promoting roles of HSP60 and HIF2α in gastric cancer cells

Original Article


The roles of HSP60 and HIF2α in diagnosis, prognosis, and prevention and treatment of various human cancers have been detected. However, the combined roles of HSP60 and HIF2α on the prognosis of patients with gastric cancer remain unclear. In this work, we confirmed that the levels of HSP60 and HIF2α messenger RNA (mRNA) and protein were higher in gastric cancer tissues than that in matched normal tissues by using real-time PCR and Western blot. Furthermore, we confirmed that inhibition of HSP60 or HIF2α could induce apoptosis and inhibit cell mobility. Co-immunoprecipitation (co-IP) was performed to determine the interaction between HSP60 and HIF2α. Lastly, we confirmed that knockdown of HSP60 or HIF2α induced apoptosis in gastric cancer cells is negatively related to the MEK/ERK signaling in vitro. In summary, HSP60 or HIF2α protein expression may be a predictive marker for the prognosis of the patients with gastric cancer. Targeting HSP60 and HIF2α could be a future strategy to improve survival of gastric patients with poor prognosis.


HIF2α HSP60 Apoptosis Mobility Survival rate 



We thank Dr. Pu Xia for technical assistance.

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Tanaka S, Arii S. Molecular targeted therapy for hepatocellular carcinoma in the current and potential next strategies. J Gastroenterol. 2011;46:289–96.CrossRefPubMedGoogle Scholar
  2. 2.
    Wenger RH, Gassmann M. Oxygen(es) and the hypoxia-inducible factor-1. Biol Chem. 1997;378:609–16.PubMedGoogle Scholar
  3. 3.
    Wang HX, Qin C, Han FY, Wang XH, Li N. HIF-2α as a prognostic marker for breast cancer progression and patient survival. Genet Mol Res. 2014;13:2817–26.CrossRefPubMedGoogle Scholar
  4. 4.
    Tong WW, Tong GH, Chen XX, Zheng HC, Wang YZ. HIF2α is associated with poor prognosis and affects the expression levels of survivin and cyclin D1 in gastric carcinoma. Int J Oncol. 2015;46:233–42.PubMedGoogle Scholar
  5. 5.
    Wu XH, Qian C, Yuan K. Correlations of hypoxia-inducible factor-1α/hypoxia-inducible factor-2α expression with angiogenesis factors expression and prognosis in non-small cell lung cancer. Chin Med J (Engl). 2011;124:11–8.Google Scholar
  6. 6.
    Cohen M, Dromard M, Petignat P. Heat shock proteins in ovarian cancer: a potential target for therapy. Gynecol Oncol. 2010;119:164–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Kaigorodova EV, Bogatyuk MV. Heat shock proteins as prognostic markers of cancer. Curr Cancer Drug Targets. 2014;14:713–26.CrossRefPubMedGoogle Scholar
  8. 8.
    Soltys BJ, Gupta RS. Mitochondrial-matrix proteins at unexpected locations: are they exported? Trends Biochem Sci. 1999;24:174–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Faried A, Sohda M, Nakajima M, Miyazaki T, Kato H, Kuwano H. Expression of heat-shock protein Hsp60 correlated with the apoptotic index and patient prognosis in human oesophageal squamous cell carcinoma. Eur J Cancer. 2004;40:2804–11.CrossRefPubMedGoogle Scholar
  10. 10.
    Cappello F, Di Stefano A, D’Anna SE, Donner CF, Zummo G. Immunopositivity of heat shock protein 60 as a biomarker of bronchial carcinogenesis. Lancet Oncol. 2005;6:816.CrossRefPubMedGoogle Scholar
  11. 11.
    Hamelin C, Cornut E, Poirier F, Pons S, Beaulieu C, Charrier JP, et al. Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer. FEBS J. 2011;278:4845–59.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Khalil AA. Biomarker discovery: a proteomic approach for brain cancer profiling. Cancer Sci. 2007;98:201–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Li XS, Xu Q, Fu XY, Luo WS. Heat shock protein 60 overexpression is associated with the progression and prognosis in gastric cancer. PLoS One. 2014;9, e107507.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Fu DZ, Cheng Y, He H, Liu HY, Liu YF. The fate of Krüppel-like factor 9-positive hepatic carcinoma cells may be determined by the programmed cell death protein 5. Int J Oncol. 2014;44:153–60.PubMedGoogle Scholar
  15. 15.
    Sena JA, Wang L, Hu CJ. BRG1 and BRM chromatin-remodeling complexes regulate the hypoxia response by acting as coactivators for a subset of hypoxia-inducible transcription factor target genes. Mol Cell Biol. 2013;33:3849–63.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Holmes MD, Chen WY, Schnitt SJ, Collins L, Colditz GA, Hankinson SE, et al. COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat. 2011;130:657–62.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Glaessgen A, Jonmarker S, Lindberg A, Nilsson B, Lewensohn R, Ekman P, et al. Heat shock proteins 27, 60 and 70 as prognostic markers of prostate cancer. APMIS. 2008;116:888–95.CrossRefPubMedGoogle Scholar
  18. 18.
    Xu X, Wang W, Shao W, Yin W, Chen H, Qiu Y, et al. Heat shock protein-60 expression was significantly correlated with the prognosis of lung adenocarcinoma. J Surg Oncol. 2011;104:598–603.CrossRefPubMedGoogle Scholar
  19. 19.
    Hjerpe E, Egyhazi S, Carlson J, Stolt MF, Schedvins K, Johansson H, et al. HSP60 predicts survival in advanced serous ovarian cancer. Int J Gynecol Cancer. 2013;23:448–55.CrossRefPubMedGoogle Scholar
  20. 20.
    Minet E, Mottet D, Michel G, Roland I, Raes M, Remacle J, et al. Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS Lett. 1999;460:251–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Chen S, Duan G, Zhang R, Fan Q. Helicobacter pylori cytotoxin-associated gene A protein upregulates α-enolase expression via Src/MEK/ERK pathway: implication for progression of gastric cancer. Int J Oncol. 2014;45:764–70.PubMedGoogle Scholar
  22. 22.
    Han XR, Sun Y, Bai XZ. The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells. Cell Signal. 2012;24:1713–21.CrossRefPubMedGoogle Scholar
  23. 23.
    Lin Z, Zhang C, Zhang M, Xu D, Fang Y, Zhou Z, et al. Targeting cadherin-17 inactivates Ras/Raf/MEK/ERK signaling and inhibits cell proliferation in gastric cancer. PLoS One. 2014;9, e85296.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Wei-Wei Tong
    • 1
  • Guang-Hui Tong
    • 1
  • Hong Kong
    • 1
  • Yong Liu
    • 1
    • 1
  1. 1.Department of Laboratory MedicineShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China

Personalised recommendations