Lysophosphatidic acid (LPA) is a small signaling phospholipid that mediates diverse functions including cell proliferation, migration and survival by engaging LPA-agonized G-protein coupled receptors. Autophagy is a survival mechanism in response to nutrient depletion or organellar damage that encloses idle or damaged organelles within autophagosomes that are then delivered to lysosomes for degradation. However, the relationship between LPA and autophagy is largely unknown. The purpose of this study is to elucidate whether LPA affects autophagy through the ERK1/2 and/or the Akt/mTOR signaling pathways. In this study, we investigated the effect of LPA on autophagy-regulating pathways in various prostate-derived cancer cells including PC3, LNCaP and Du145 cells grown in complete medium and exposed to serum-free medium. Using Western blotting and ELISA, we determined that LPA stimulates the ERK and mTOR pathways in complete and serum-free medium. The mTOR pathway led to phosphorylation of S6K and ULK, which respectively stimulates protein synthesis and arrests autophagy. Consistent with this, LPA exposure suppressed autophagy as measured by LC3 maturation and formation of GFP-LC3 puncta. Altogether, these results suggest that LPA suffices to activate mTORC1 and suppress autophagy in prostate cancer cells.
Biochemistry and cell biology = Biochimie et biologie cellulaire. 2018 Nov 07 [Epub ahead of print]
Gizem Esra Genc, Victoria E B Hipolito, Roberto J Botelho, Saadet Gumuslu
Akdeniz University, Faculty of Medicine, Department of Medical Biochemistry, Antalya, Turkey ; ., Ryerson University, Department of Chemistry and Biology and the Graduate Program in Molecular Science, Toronto, Ontario, Canada ; ., Ryerson University, Department of Chemistry and Biology and the Graduate Program in Molecular Science, Toronto, Ontario, Canada ; ., Akdeniz University, Faculty of Medicine, Department of Medical Biochemistry, Antalya, Turkey ; .