Loss of PTEN stabilizes the lipid modifying enzyme cytosolic phospholipase A₂α via AKT in prostate cancer cells

Aberrant increase in pAKT, due to a gain-of-function mutation of PI3K or lossof-function mutation or deletion of PTEN, occurs in prostate cancer and is associated with poor patient prognosis. Cytosolic phospholipase A2a (cPLA2a) is a lipid modifying enzyme by catalyzing the hydrolysis of membrane arachidonic acid. Arachidonic acid and its metabolites contribute to survival and proliferation of prostate cancer cells. We examined whether AKT plays a role in promoting cPLA2a action in prostate cancer cells. We found a concordant increase in pAKT and cPLA2a levels in prostate tissue of prostate epithelial-specific PTEN-knockout but not PTEN-wide type mice. Restoration of PTEN expression or inhibition of PI3K action decreased cPLA2a expression in PTENmutated or deleted prostate cancer cells. An increase in AKT by Myr-AKT elevated cPLA2a protein levels, which could be diminished by inhibition of AKT phosphorylation without noticeable change in total AKT levels. pAKT levels had no influence on cPLA2a at mRNA levels but reduced cPLA2a protein degradation. Anti-AKT antibody coimmunoprecipitated cPLA2a and vice versa. Hence, AKT plays a role in enhancing cPLA2a protein stability in PTEN-null prostate cancer cells, revealing a link between oncogenic pathway and lipid metabolism