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. 2016 Jun 16;7(29):46321–46334. doi: 10.18632/oncotarget.10113

Figure 2. Cav-1 regulated ACC1 and FASN expression in PCa cells in an AR-independent manner at the transcriptional level, promoting palmitate synthesis.

Figure 2

A. Androgen deprivation decreased the phosphorylation of AR, AR, and FASN protein levels in LNCaP cells. Cav-1 induction increased the phosphorylation of AR, AR, ACC1, and FASN protein levels in the presence and absence of R1881. B. Androgen deprivation increased the phosphorylation and total protein levels of AR and decreased the FASN and ACC1 protein levels in VCaP cells. Downregulation of Cav-1 decreased the phosphorylation and total levels of AR in the presence and absence of androgens. In addition, downregulation of Cav-1 decreased the protein levels of FASN and ACC1 synergistically with androgen deprivation. C. Androgen deprivation decreased the phosphorylation and protein levels of AR but only mildly affected the FASN and ACC1 protein levels in LNCaP (c+) cells. Cav-1 knockdown decreased the phosphorylation and protein levels of AR synergistically with androgen deprivation and significantly decreased the FASN and ACC1 protein levels. D. Induction of Cav-1 increased the protein levels of FASN and ACC1, and knockdown of AR decreased the levels of these proteins in LNCaP cells. Induction of Cav-1 in the absence of AR increased the levels of these proteins, suggesting that Cav-1 promotes the expression of FASN and ACC1 independently of AR. E. Cav-1 knockdown decreased expression of ACC1 and FASN in PC-3 cells. F. Downregulation of Cav-1 led to decreased protein levels of ACC1 and FASN in PC-3M cells. G. In the presence of androgens Cav-1 induction increased the RNA levels of FASN (p<0.001) in LNCaP cells. In the absence of androgens, Cav-1 induction increased the RNA levels of ACC1 (p<0.001) and FASN (p=0.026). H. The downregulation of Cav-1 led to significantly lower RNA levels of ACC1 (P<0.001 for both Cav-1siRNA6 and Cav-1siRNA8) and FASN (P<0.001 for both Cav-1siRNA6 and Cav-1siRNA8) in PC-3M cells. I. Palmitate measurements showed that in the absence of androgens, Cav-1 induction increased the levels of palmitate (P=0.041) in LNCaP cells. J. Cav-1 knockdown significantly reduced palmitate levels (P=0.01) in PC-3M cells.