Skip to main content
SpringerLink
Log in

TMEM49-related apoptosis and metastasis in ovarian cancer and regulated cell death

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Ovarian cancer is one of the greatest causes of cancer death in women. The association of TMEM49 and ovarian cancer is poorly defined. Here, we reported that TMEM49 was significantly increased in ovarian tumor tissues compared to ovarian normal tissues. Furthermore, down-regulation of TMEM49 through RNA interference inhibited cell proliferation and arrested G1/S transition in two ovarian cancer cell lines, OVCAR3 and A2780. More importantly, TMEM49 silencing induced cell apoptosis. Additionally, down-regulation of TMEM49 in ovarian cancer notably repressed cell invasion and adhesion. Further gene set enrichment analysis suggested that apoptosis and metastasis up related signal pathways were associated with the TMEM49 expression. Western blot revealed that the expression of Caspase3, Bad, and Bax were increased, while expression of MMP2, KLF10, and CXCL12 were reduced by TMEM49 knockdown. Since expression of TMEM49 seems to be associated with the apoptosis and metastasis up signaling pathways of ovarian cancer, and suppression of its expression can inhibit cancer cell growth and metastasis, TMEM49 may be a potential therapeutic target in human ovarian cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386

    Article  CAS  PubMed  Google Scholar 

  2. Banerjee S, Kaye SB (2013) New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res 19(5):961–968

    Article  CAS  PubMed  Google Scholar 

  3. Aunoble B, Sanches R, Didier E, Bignon Y (2000) Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review). Int J Oncol 16(3):567–643

    CAS  PubMed  Google Scholar 

  4. Suzuki S, Moore DH, Ginzinger DG, Godfrey TE, Barclay J, Powell B, Pinkel D, Zaloudek C, Lu K, Mills G (2000) An approach to analysis of large-scale correlations between genome changes and clinical endpoints in ovarian cancer. Cancer Res 60(19):5382–5385

    CAS  PubMed  Google Scholar 

  5. Pardo R, Lo Ré A, Archange C, Ropolo A, Papademetrio DL, Gonzalez CD, Alvarez EM, Iovanna JL, Vaccaro MI (2010) Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells. Pancreatology 10(1):19–26

    Article  CAS  PubMed  Google Scholar 

  6. Molejon MI, Ropolo A, Vaccaro MI (2013) VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation. Autophagy 9(6):933–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Dusetti NJ, Jiang Y, Vaccaro MI, Tomasini R, Samir AA, Calvo EL, Ropolo A, Fiedler F, Mallo GV, Dagorn J-C (2002) Cloning and expression of the rat vacuole membrane protein 1 (VMP1), a new gene activated in pancreas with acute pancreatitis, which promotes vacuole formation. Biochem Biophys Res Commun 290(2):641–649

    Article  CAS  PubMed  Google Scholar 

  8. Guo L, Yang LY, Fan C, Chen GD, Wu F (2012) Novel roles of Vmp1: inhibition metastasis and proliferation of hepatocellular carcinoma. Cancer Sci 103(12):2110–2119

    Article  CAS  PubMed  Google Scholar 

  9. Grasso D, Ropolo A, Lo Re A, Boggio V, Molejon MI, Iovanna JL, Gonzalez CD, Urrutia R, Vaccaro MI (2011) Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. J Biol Chem 286(10):8308–8324. doi:10.1074/jbc.M110.197301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ropolo A, Grasso D, Pardo R, Sacchetti ML, Archange C, Re AL, Seux M, Nowak J, Gonzalez CD, Iovanna JL (2007) The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells. J Biol Chem 282(51):37124–37133

    Article  CAS  PubMed  Google Scholar 

  11. Sauermann M, Sahin Ö, Sültmann H, Hahne F, Blaszkiewicz S, Majety M, Zatloukal K, Füzesi L, Poustka A, Wiemann S (2008) Reduced expression of vacuole membrane protein 1 affects the invasion capacity of tumor cells. Oncogene 27(9):1320–1326

    Article  CAS  PubMed  Google Scholar 

  12. Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA 64(1):9–29

    Article  PubMed  Google Scholar 

  13. Grasso D, Sacchetti ML, Bruno L, Lo Re A, Iovanna JL, Gonzalez CD, Vaccaro MI (2009) Autophagy and VMP1 expression are early cellular events in experimental diabetes. Pancreatology 9(1–2):81–88. doi:10.1159/000178878

    Article  CAS  PubMed  Google Scholar 

  14. Qian Q, Zhou H, Chen Y, Shen C, He S, Zhao H, Wang L, Wan D, Gu W (2014) VMP1 related autophagy and apoptosis in colorectal cancer cells: vMP1 regulates cell death. Biochem Biophys Res Commun 443(3):1041–1047

    Article  CAS  PubMed  Google Scholar 

  15. Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP (2007) GSEA-P: a desktop application for gene set enrichment analysis. Bioinformatics 23(23):3251–3253

    Article  CAS  PubMed  Google Scholar 

  16. Porter AG, Jänicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6(2):99–104

    Article  CAS  PubMed  Google Scholar 

  17. Danial NN, Gramm CF, Scorrano L, Zhang C-Y, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424(6951):952–956

    Article  CAS  PubMed  Google Scholar 

  18. Oltval ZN, Milliman CL, Korsmeyer SJ (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell 74(4):609–619

    Article  Google Scholar 

  19. Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J 278(1):16–27

    Article  CAS  PubMed  Google Scholar 

  20. Subramaniam M, Hawse JR, Rajamannan NM, Ingle JN, Spelsberg TC (2010) Functional role of KLF10 in multiple disease processes. Biofactors 36(1):8–18

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Scotton CJ, Wilson JL, Scott K, Stamp G, Wilbanks GD, Fricker S, Bridger G, Balkwill FR (2002) Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res 62(20):5930–5938

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Grant support was provided by Natural Science Foundation of Fujian Province, China (Grant No. 2013J01324).

Author information

Author notes

    Authors and Affiliations

    1. FuJian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China

      Lili Zheng

    2. Department of Gynecology, The Second Hospital of Fuzhou Affiliated to Xiamen University, Fuzhou, 350007, People’s Republic of China

      Lingling Chen

    3. Department of Gynecology, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, No. 602, 817 Middle Road, Taijiang District, Fuzhou, 350007, People’s Republic of China

      Xuan Zhang, Jingfen Zhan & Jie Chen

    Authors
    1. Lili Zheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Lingling Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Xuan Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jingfen Zhan
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Jie Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Jie Chen.

    Ethics declarations

    Conflict of interest

    The authors declare no competing financial interests.

    Additional information

    Lili Zheng and Lingling Chen have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zheng, L., Chen, L., Zhang, X. et al. TMEM49-related apoptosis and metastasis in ovarian cancer and regulated cell death. Mol Cell Biochem 416, 1–9 (2016). https://doi.org/10.1007/s11010-016-2684-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11010-016-2684-3

    Keywords

    Search

    Navigation