Background: Activation of Akt and increased expression of integrin β3 are the two most important changes that have been linked to the attainment of metastatic potential by prostate cancer cells.
However, a direct link between Akt activity and inside-out activation of integrin β3in mediating prostate cancer cell metastatic properties is not established.
Methods:Using functional and biochemical approaches, we examined the role of Akt1 in the affinity modulation of integrin β3in prostate cancer cells.
Results:Although expression of murine TRAMP and human PC3 cells with constitutively active Akt1 (CA-Akt1) enhanced their affinity for integrin αvβ3 specific ligands and motility on various extracellular matrix proteins, the reverse was observed with the expression of dominant-negative Akt1 (DN-Akt1). Although enhanced motility and transendothelial migration of CA-Akt1-expressing cells were blunted by co-expression with DN-integrin β3 or upon pre-treatment with integrin β3-blocking antibodies (LM 609), impaired motility and transendothelial migration of DN-Akt1-expressing cells were rescued by pre-treatment of prostate cancer cells with integrin β3-activating antibodies, AP7.4.
Conclusion:Our data is the first to demonstrate a link between Akt1 activity and affinity modulation of integrin β3 in the regulation of prostate cancer cell motility, transendothelial migration and chemotaxis to metastatic stimuli.
Written by:
Goc A, Liu J, Byzova TV, Somanath PR. Are you the author?
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Georgia Health Sciences University, HM1200, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
Reference: Br J Cancer. 2012 Aug 7;107(4):713-23.
doi: 10.1038/bjc.2012.295
PubMed Abstract
PMID: 22767145
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