Research Papers:

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

Soma Vignarajan _, Chanlu Xie, Mu Yao, Yuting Sun, Ulla Simanainen, Paul Sved, Tao Liu and Qihan Dong

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2014; 5:6289-6299. https://doi.org/10.18632/oncotarget.2198

Metrics: PDF 2619 views  |   HTML 3799 views  |   ?  


Soma Vignarajan1, Chanlu Xie1,6, Mu Yao1, Yuting Sun2, Ulla Simanainen3, Paul Sved4, Tao Liu2,5, Qihan Dong1,6

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


Qihan Dong, email:

Keywords: cytosolic phospholipase A2, AKT, PTEN, prostate cancer

Received: June 06, 2014 Accepted: July 07, 2014 Published: July 09, 2014


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 A2α (cPLA2α) 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 cPLA2α action in prostate cancer cells. We found a concordant increase in pAKT and cPLA2α 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 cPLA2α expression in PTEN-mutated or deleted prostate cancer cells. An increase in AKT by Myr-AKT elevated cPLA2α protein levels, which could be diminished by inhibition of AKT phosphorylation without noticeable change in total AKT levels. pAKT levels had no influence on cPLA2α at mRNA levels but reduced cPLA2α protein degradation. Anti-AKT antibody co-immunoprecipitated cPLA2α and vice versa. Hence, AKT plays a role in enhancing cPLA2α protein stability in PTEN-null prostate cancer cells, revealing a link between oncogenic pathway and lipid metabolism.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 2198