Figure 6. Cav-1, ACC1 and FASN expression in human primary prostate tumors and bone metastases.

Cav-1 expression was associated with ACC1 expression and elevated levels of palmitoleate and oleate in the bone marrow aspirates from mCRPC were associated with worse response to abiraterone acetate. A. Cav-1, ACC1and FASN expressions are significantly increased in metastatic PCa compared to primary treated and untreated PCa. P-values are shown in the figure. B. Left panel: Cav-1- PCa cells had minimal level of ACC1 (top row); the Cav-1+ cancer cells exhibited strong ACC1 immunostaining (middle row), whereas FASN immunostaining was not reduced in the area with low Cav-1 (bottom row). Original magnification: 200x. Right panel: the average ACC1 immunostaining score in the Cav-1+ PCa was significantly higher than that in the Cav-1–area of the same PCa tissue (P=0.015); data are plotted as means± SEM. P value was from by paired sign test. C. Long-chain fatty acids were measured in bone marrow aspirations from patients with mCRPC treated with Abiraterone Acetate (AA). Two products of palmitate (palmitoleate and oleate) were found to be higher at 8 weeks of treatment in non-responders to AA compared to responders (p=0.015-palmitoleate and p=0.045-oleate). D. Schematic summary of our findings: AR is activated by androgens and promotes the expression of ACC1 and FASN, which mediate the synthesis of long-chain fatty acids including palmitoleate and oleate leading to PCa cell growth. Under androgen deprivation therapy (ADT), Cav-1 is upregulated and phosphorylates AR on the serine 81 residue. Cav-1 upregulation also increases the expression of ACC1 and FASN, promoting fatty acid synthesis and PCa cell growth under conditions of androgen deprivation.