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

// Soma Vignarajan 1 , Chanlu Xie 1,6 , Mu Yao 1 , Yuting Sun 2 , Ulla Simanainen 3 , Paul Sved 4 , Tao Liu 2,5 , Qihan Dong 1,6 1 Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia 2 Children’s Cancer Institute Australia for Medical Research, Sydney, Australia 3 ANZAC Research institute, The University of Sydney, Sydney, NSW, Australia 4 Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia 5 School of Women’s and Children’s Health, UNSW Medicine, Sydney, Australia, Australia 6 School of Science and Health, The University of Western Sydney, Sydney, Australia Correspondence: Qihan Dong, email: // Keywords : cytosolic phospholipase A2, AKT, PTEN, prostate cancer Received : June 06, 2014 Accepted : July 07, 2014 Published : July 09, 2014 Abstract Aberrant increase in pAKT, due to a gain-of-function mutation of PI3K or loss-of-function mutation or deletion of PTEN, occurs in prostate cancer and is associated with poor patient prognosis. Cytosolic phospholipase A 2 α (cPLA 2 α) 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 cPLA 2 α action in prostate cancer cells. We found a concordant increase in pAKT and cPLA 2 α 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 cPLA 2 α expression in PTEN -mutated or deleted prostate cancer cells. An increase in AKT by Myr-AKT elevated cPLA 2 α protein levels, which could be diminished by inhibition of AKT phosphorylation without noticeable change in total AKT levels. pAKT levels had no influence on cPLA 2 α at mRNA levels but reduced cPLA 2 α protein degradation. Anti-AKT antibody co-immunoprecipitated cPLA 2 α and vice versa. Hence, AKT plays a role in enhancing cPLA 2 α protein stability in PTEN-null prostate cancer cells, revealing a link between oncogenic pathway and lipid metabolism.