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Activation of Rap1 promotes prostate cancer metastasis.

Publication ,  Journal Article
Bailey, CL; Kelly, P; Casey, PJ
Published in: Cancer Res
June 15, 2009

Elucidating the mechanisms of prostate cancer (CaP) survival and metastasis are critical to the discovery of novel therapeutic targets. The monomeric G protein Rap1 has been implicated in cancer tumorigenesis. Rap1 signals to pathways involved in cell adhesion, migration, and survival, suggesting Rap1 may promote several processes associated with cancer cell metastasis. Examination of CaP cell lines revealed cells with a high metastatic ability exhibited increased Rap1 activity and reduced expression of the negative regulator Rap1GAP. Rap1 can be further stimulated in these cells by stromal-derived factor (SDF-1), an agonist known to regulate tumor cell metastasis and tropism to bone. Activation of Rap1 increased CaP cell migration and invasion, and inhibition of Rap1A activity via RNAi-mediated knockdown or ectopic expression of Rap1GAP markedly impaired CaP cell migration and invasion. Additional studies implicate integrins alpha4, beta3, and alphavbeta3 in the mechanism of Rap1-mediated CaP migration and invasion. Extending the effect of Rap1 activity in CaP metastasis in vivo, introduction of activated Rap1 into CaP cells dramatically enhanced the rate and incidence of CaP metastasis in a xenograft mouse model. These studies provide compelling evidence to support a role for aberrant Rap1 activation in CaP progression, and suggest that targeting Rap1 signaling could provide a means to control metastatic progression of this cancer.

Duke Scholars

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2009

Volume

69

Issue

12

Start / End Page

4962 / 4968

Location

United States

Related Subject Headings

  • rap1 GTP-Binding Proteins
  • RNA Interference
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Male
  • Humans
  • Cell Movement
  • Cell Line, Tumor
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bailey, C. L., Kelly, P., & Casey, P. J. (2009). Activation of Rap1 promotes prostate cancer metastasis. Cancer Res, 69(12), 4962–4968. https://doi.org/10.1158/0008-5472.CAN-08-4269
Bailey, Candice L., Patrick Kelly, and Patrick J. Casey. “Activation of Rap1 promotes prostate cancer metastasis.Cancer Res 69, no. 12 (June 15, 2009): 4962–68. https://doi.org/10.1158/0008-5472.CAN-08-4269.
Bailey CL, Kelly P, Casey PJ. Activation of Rap1 promotes prostate cancer metastasis. Cancer Res. 2009 Jun 15;69(12):4962–8.
Bailey, Candice L., et al. “Activation of Rap1 promotes prostate cancer metastasis.Cancer Res, vol. 69, no. 12, June 2009, pp. 4962–68. Pubmed, doi:10.1158/0008-5472.CAN-08-4269.
Bailey CL, Kelly P, Casey PJ. Activation of Rap1 promotes prostate cancer metastasis. Cancer Res. 2009 Jun 15;69(12):4962–4968.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

June 15, 2009

Volume

69

Issue

12

Start / End Page

4962 / 4968

Location

United States

Related Subject Headings

  • rap1 GTP-Binding Proteins
  • RNA Interference
  • Prostatic Neoplasms
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoplasm Invasiveness
  • Male
  • Humans
  • Cell Movement
  • Cell Line, Tumor