title: Loss of PTEN stabilizes the lipid modifying enzyme cytosolic phospholipase A₂α via AKT in prostate cancer cells.
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 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.
authors.affiliation: Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Soma
authors.initials: S
authors.lastname: Vignarajan
authors.affiliation: Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Science and Health, The University of Western Sydney, Sydney, Australia.
authors.forename: Chanlu
authors.initials: C
authors.lastname: Xie
authors.affiliation: Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Mu
authors.initials: M
authors.lastname: Yao
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Sydney, Australia.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Sun
authors.affiliation: ANZAC Research institute, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Ulla
authors.initials: U
authors.lastname: Simanainen
authors.affiliation: Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Sved
authors.affiliation: Children's Cancer Institute Australia for Medical Research, Sydney, Australia; School of Women's and Children's Health, UNSW Medicine, Sydney, Australia, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Discipline of Endocrinology, Central Clinical School, Bosch Institute, Royal Prince Alfred Hospital, and Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Science and Health, The University of Western Sydney, Sydney, Australia.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Dong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D054467:Phospholipases A2; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487757:Pten protein, mouse