Skip to main content

Advertisement

SpringerLink
Log in

The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Rab31, a member of the Ras superfamily, is reported to play a role in tumor development and progression. However, the detailed role of Rab31 in proliferation and apoptosis of cancer cells is still unclear. Here, we used different cell lines, such as glioblastoma, and cervical cancer, to investigate the role of Rab31 in cancer progression. We found that Rab31 promotes U87 and SiHa cell proliferation via activation of G1/S checkpoint transitions, accompanied with an increase of cyclin D1, cyclin A, and cyclin B1. Meanwhile, Rab31 inhibits U87 and SiHa cell apoptosis, and decreased the BAX and PIG3 expression, but enhanced BCL2 expression. In addition, Rab31 induces N-cadherin, Vimentin, and Snail expression, and inhibits E-cadherin expression to regulate proliferation and migration. Besides, we observed that ERK1/2 and PI3k/AKT pathways are required for Rab31-induced cell proliferation and migration. In vivo, the knockdown of Rab31 suppresses tumor mass growth. In conclusion, our data highlight the crucial role of Rab31 in cancer progression, proliferation, and apoptosis, and indicates that Rab31 may be a useful and effective target for the clinical therapy of most cancers.

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

Similar content being viewed by others

References

  1. Cheng KW, Lahad JP, Gray JW et al (2005) Emerging role of rabgtpases in cancer and human disease. Cancer Res 65:2516–2519

    Article  CAS  PubMed  Google Scholar 

  2. Chua CE, Tang BL (2015) The role of the small gtpase rab31 in cancer. J Cell Mol Med 19:1–10

    Article  CAS  PubMed  Google Scholar 

  3. Jin C, Rajabi H, Pitroda S, Li A et al (2012) Cooperative interaction between the muc1-c oncoprotein and the rab31 gtpase in estrogen receptor-positive breast cancer cells. PLoS ONE 7:e39432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grismayer B, Solch S, Seubert B et al (2012) Rab31 expression levels modulate tumor-relevant characteristics of breast cancer cells. Mol Cancer 11:62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kotzsch M, Dorn J, Doetzer K et al (2011) Mrna expression levels of the biological factors upar, upardel4/5, and rab31, displaying prognostic value in breast cancer, are not clinically relevant in advanced ovarian cancer. Biol Chem 392:1047–1051

    Article  CAS  PubMed  Google Scholar 

  6. Serao NV, Delfino KR, Southey BR et al (2011) Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival. BMC Med Genom 4:49

    Article  CAS  Google Scholar 

  7. Kunkle BW, Yoo C, Roy D (2013) Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma. PLoS ONE 8:e64140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Woolf EC, Scheck AC (2012) Metabolism and glioma therapy. CNS Oncol 1(1):7–10

    Article  CAS  PubMed  Google Scholar 

  9. Vehlow A, Cordes N (1836) Invasion as target for therapy of glioblastoma multiforme. Biochim Biophys Acta 2013:236–244

    Google Scholar 

  10. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  CAS  PubMed  Google Scholar 

  11. Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):S4–S66

    Article  PubMed  Google Scholar 

  12. Waggoner SE (2003) Cervical cancer. Lancet 361:2217–2225

    Article  PubMed  Google Scholar 

  13. Miyazawa J, Mitoro A, Kawashiri S et al (2004) Expression of mesenchyme-specific gene Rab31 in squamous cell carcinomas of the oral cavity. Cancer Res 64:2024–2029

    Article  CAS  PubMed  Google Scholar 

  14. Shell S, Park SM, Radjabi AR et al (2007) Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci U S A 104:11400–11405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Langelotz C, Schmid P, Jakob C et al (2003) Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer. Br J Cancer 88:1406–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sakamoto H, Sakamaki T, Kanda T et al (2004) Vascular endothelial growth factor is an autocrine growth factor for cardiac myxoma cells. Circ J 68:488–493

    Article  CAS  PubMed  Google Scholar 

  17. Hata AN, Engelman JA, Faber AC (2015) The BCL2 family: key mediators of the apoptotic response to targeted anticancer therapeutics. Cancer Discov 5(5):475–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Malumbres M, Barbacid M (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9:153–166

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We greatly thank other members of our lab for valuable suggestions and writing.

Conflicts of Interest

The authors indicated no potential conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, Affiliated Hospital of Shandong Academy of Medical Sciences, 38# Wuyingshan Road, 250031, Jinan, Shandong, China

    Yunyan Pan, Lijun Chen, Yan Liu, Yanlin Feng & Junyuan Yan

  2. Department of Gynaecology and Obstetrics, The Third People’s Hospital of Jinan City, Jinan, Shandong, China

    Yanling Zhang

Authors
  1. Yunyan Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanling Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lijun Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanlin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junyuan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junyuan Yan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pan, Y., Zhang, Y., Chen, L. et al. The Critical Role of Rab31 in Cell Proliferation and Apoptosis in Cancer Progression. Mol Neurobiol 53, 4431–4437 (2016). https://doi.org/10.1007/s12035-015-9378-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-015-9378-9

Keywords

Search

Navigation