title: Akt1 mediates prostate cancer cell microinvasion and chemotaxis to metastatic stimuli via integrin β₃ affinity modulation.
abstract: BACKGROUND
  Activation of Akt and increased expression of integrin β(3) 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 β(3) in 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 β(3) in prostate cancer cells.
  
  
  RESULTS
  Although expression of murine TRAMP and human PC3 cells with constitutively active Akt1 (CA-Akt1) enhanced their affinity for integrin α(v)β(3) 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 β(3) or upon pre-treatment with integrin β(3)-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 β(3)-activating antibodies, AP7.4.
  
  
  CONCLUSIONS
  Our data is the first to demonstrate a link between Akt1 activity and affinity modulation of integrin β(3) in the regulation of prostate cancer cell motility, transendothelial migration and chemotaxis to metastatic stimuli.
authors: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Georgia Health Sciences University, HM1200, Augusta, GA 30912, USA.
authors: A
authors: A
authors: Goc
authors: J
authors: J
authors: Liu
authors: T V
authors: TV
authors: Byzova
authors: P R
authors: PR
authors: Somanath
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002633:Chemotaxis; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D061206:Neoplasm Micrometastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D039661:Integrin beta3; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt