Abstract A073: Metabolism of saturated fatty acids accelerates Src-mediated prostate tumor progression

Abstract

Abstract The association of dietary fatty acids (FAs) with the risk of aggressive prostate cancer is controversial. The mechanisms of supporting how dietary FAs promote cancer progression are largely unknown. The expression and/or activity of Src family kinases are frequently elevated in several cancers, including advanced prostate cancer. This study demonstrates that dietary FAs accelerated Src-mediated prostate tumorigenesis and prostate cancer cell growth in vivo. Additionally, high dietary fat compromised the ability of dasatinib to block the oncogenic signaling of Src kinase. Metabolism of exogenous FAs, in particular palmitic and myristic acids, increased biosynthesis of acyl-CoAs and altered ceramide levels, in particular C16:0 ceramide. The combination of these effects elevated levels of myristoylated Src, increased the amount of Src in detergent resistant membranes, and enhanced Src kinase mediated oncogenic signaling. Targeting myristoylation of Src kinase, which is required for its association at the cellular membrane, blocked high fat diet-accelerated tumorigenesis in vivo. These findings illustrate how the metabolism of saturated FAs can accelerate Src-driven prostate tumor progression and suggest that prostate cancer survivors may benefit from a diet low in saturated fat. Citation Format: SUNGJIN KIM, Xiangkun Yang, Qianjin Li, Meng Wu, Zanna Beharry, Michael Bartlett, Alicja Bielawska, Houjian Cai. Metabolism of saturated fatty acids accelerates Src-mediated prostate tumor progression [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A073.