Document Detail


Activation of Rap1 promotes prostate cancer metastasis.
MedLine Citation:
PMID:  19470770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Candice L Bailey; Patrick Kelly; Patrick J Casey
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-05-26
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-16     Completed Date:  2009-07-06     Revised Date:  2014-10-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4962-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Adhesion
Cell Line, Tumor
Cell Movement
Humans
Male
Neoplasm Invasiveness
Neoplasm Metastasis*
Prostatic Neoplasms / metabolism*,  pathology
RNA Interference
rap1 GTP-Binding Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
CA100869/CA/NCI NIH HHS; R01 CA100869/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 3.6.5.2/rap1 GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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