SpringerLink
Log in

Rap2B promotes migration and invasion of human suprarenal epithelioma

  • Research Article
  • Published:
Tumor Biology

Abstract

The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29. doi:10.3322/caac.20138.

    Article  PubMed  Google Scholar 

  2. Mohammed A, Shergill I, Little B. Management of metastatic renal cell carcinoma: current trends. Expert Rev Mol Diagn. 2009;9(1):75–83. doi:10.1586/14737159.9.1.75.

    Article  PubMed  Google Scholar 

  3. Kausch I, Jiang H, Ewerdwalbesloh N, Doehn C, Kruger S, Sczakiel G, et al. Inhibition of Ki-67 in a renal cell carcinoma severe combined immunodeficiency disease mouse model is associated with induction of apoptosis and tumour growth inhibition. BJU Int. 2005;95(3):416–20. doi:10.1111/j.1464-410X.2005.05312.x.

    Article  CAS  PubMed  Google Scholar 

  4. Janzen NK, Kim HL, Figlin RA, Belldegrun AS. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin N Am. 2003;30(4):843–52.

    Article  Google Scholar 

  5. Ohmstede CA, Farrell FX, Reep BR, Clemetson KJ, Lapetina EG. RAP2B: a RAS-related GTP-binding protein from platelets. Proc Natl Acad Sci U S A. 1990;87(17):6527–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Farrell FX, Ohmstede CA, Reep BR, Lapetina EG. cDNA sequence of a new Ras-related gene (Rap2B) isolated from human platelets with sequence homology to rap2. Nucleic Acids Res. 1990;18(14):4281.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zhang X, He Y, Lee KH, Dubois W, Li Z, Wu X, et al. Rap2B, a novel p53 target, regulates p53-mediated pro-survival function. Cell Cycle. 2013;12(8):1279–91. doi:10.4161/cc.24364. Georgetown, Tex.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. ** TG, Satoh T, Liao Y, Song C, Gao X, Kariya K, et al. Role of the CDC25 homology domain of phospholipase C epsilon in amplification of Rap1-dependent signaling. J Biol Chem. 2001;276(32):30301–7. doi:10.1074/jbc.M103530200.

    Article  CAS  PubMed  Google Scholar 

  9. Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C(epsilon): a novel Ras effector. EMBO J. 2001;20(4):743–54. doi:10.1093/emboj/20.4.743.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Kelley GG, Reks SE, Smrcka AV. Hormonal regulation of phospholipase C epsilon through distinct and overlap** pathways involving G12 and Ras family G-proteins. Biochem J. 2004;378(Pt 1):129–39. doi:10.1042/bj20031370.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, et al. Regulation of a novel human phospholipase C, PLC epsilon, through membrane targeting by Ras. J Biol Chem. 2001;276(4):2752–7. doi:10.1074/jbc.M008324200.

    Article  CAS  PubMed  Google Scholar 

  12. Song C, Satoh T, Edamatsu H, Wu D, Tadano M, Gao X, et al. Differential roles of Ras and Rap1 in growth factor-dependent activation of phospholipase C epsilon. Oncogene. 2002;21(53):8105–13. doi:10.1038/sj.onc.1206003.

    Article  CAS  PubMed  Google Scholar 

  13. Bourguignon LY, Gilad E, Brightman A, Diedrich F, Singleton P. Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells. J Biol Chem. 2006;281(20):14026–40. doi:10.1074/jbc.M507734200.

    Article  CAS  PubMed  Google Scholar 

  14. Bai J, Mei PJ, Liu H, Li C, Li W, Wu YP, et al. BRG1 expression is increased in human glioma and controls glioma cell proliferation, migration and invasion in vitro. J Cancer Res Clin Oncol. 2012;138(6):991–8. doi:10.1007/s00432-012-1172-8.

    Article  CAS  PubMed  Google Scholar 

  15. Hannon GJ. RNA interference. Nature. 2002;418(6894):244–51. doi:10.1038/418244a.

    Article  CAS  PubMed  Google Scholar 

  16. Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods. 2002;26(2):199–213. doi:10.1016/s1046-2023(02)00023-3. San Diego, Calif.

    Article  CAS  PubMed  Google Scholar 

  17. Torti M, Lapetina EG. Structure and function of rap proteins in human platelets. Thromb Haemost. 1994;71(5):533–43.

    CAS  PubMed  Google Scholar 

  18. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J Cell Mol Med. 2005;9(2):267–85.

    Article  CAS  PubMed  Google Scholar 

  19. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 2006;25(1):9–34. doi:10.1007/s10555-006-7886-9.

    Article  CAS  PubMed  Google Scholar 

  20. Badiga AV, Chetty C, Kesanakurti D, Are D, Gujrati M, Klopfenstein JD, et al. MMP-2 siRNA inhibits radiation-enhanced invasiveness in glioma cells. PLoS One. 2011;6(6):e20614. doi:10.1371/journal.pone.0020614.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Overall CM, Kleifeld O. Tumour microenvironment—opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006;6(3):227–39. doi:10.1038/nrc1821.

    Article  CAS  PubMed  Google Scholar 

  22. Jung CH, Kim EM, Park JK, Hwang SG, Moon SK, Kim WJ, et al. Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncol Rep. 2013;29(6):2109–13. doi:10.3892/or.2013.2381.

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Lu CY, Lai SC. Induction of matrix metalloproteinase-2 and −9 via Erk1/2-NF-κB pathway in human astroglia infected with Toxoplasma gondii. Acta Trop. 2013;127(1):14–20. doi:10.1016/j.actatropica.2013.03.004.

    Article  CAS  PubMed  Google Scholar 

  24. Bae IH, Park MJ, Yoon SH, Kang SW, Lee SS, Choi KM, et al. Bcl-w promotes gastric cancer cell invasion by inducing matrix metalloproteinase-2 expression via phosphoinositide 3-kinase, Akt, and Sp1. Cancer Res. 2006;66:4991–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NO. 81201637, NO.81071831 and NO. 81272207), Jiehui Di was sponsored by Qing Lan Project of Jiangsu Province.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Jie-Hui Di, De-Bao Qu, Zheng Lu, Lian-Tao Li, Qian Cheng, Yong ** Zhang & Jun-Nian Zheng

  2. The Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China

    De-Bao Qu, Long-Zhen Zhang & Jun-Nian Zheng

  3. Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, School of Medicine, The University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC, 27514, USA

    Yan** Zhang

Authors
  1. Jie-Hui Di
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. De-Bao Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zheng Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lian-Tao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qian Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yong **n
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Long-Zhen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yan** Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jun-Nian Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yan** Zhang or Jun-Nian Zheng.

Additional information

Jie-Hui Di and De-Bao Qu 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

Di, JH., Qu, DB., Lu, Z. et al. Rap2B promotes migration and invasion of human suprarenal epithelioma. Tumor Biol. 35, 9387–9394 (2014). https://doi.org/10.1007/s13277-014-2174-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2174-8

Keywords

Search

Navigation