Interplay of PKD3 with SREBP1 Promotes Cell Growth via Upregulating Lipogenesis in Prostate Cancer Cells

Abstract

Protein kinase D (PKD) has been implicated in cancer cell survival, proliferation, migration and angiogenesis. However, it is still unknown whether PKD regulates cell proliferation through lipid metabolism in cancer cells. Here we report a novel function of PKD3, a member of PKD family, in regulating of prostate cancer cell proliferation by modulation of SREBP1-mediated <i>de novo</i> lipogenesis. We show that silencing of PKD3 significantly reduces lipid content and expression of the lipogenic genes encoding FASN and ATP-citrate lyase (ACLY). Moreover, endogenous PKD3 interacts with sterol regulatory element binding protein 1(SREBP1) in DU145 cells. Interestingly, PKD3 silencing decreases not only the level of matured-SREBP1 (68KD) but also the binding of SREBP1 to the promoter of <i>fasn</i> gene. In addition, overexpression of SREBP1 reverses the suppression of cell growth caused by PKD3 depletion. Finally, immune-histochemical staining indicate that PKD3 expression is positively correlated with expression of FASN and SREBP1 in prostate cancers. Taken together, these data suggest that targeting PKD3-mediated <i>de novo</i> lipogenesis may be a potential therapeutic approach to block prostate cancer progression.