Abstract A81: Targeting of free fatty acid signaling in ovarian cancer may serve as a potential therapeutic approach.

摘要: Recent studies have revealed an association between adipocyte driven free fatty acids (FFA) and the aggressiveness of epithelial ovarian cancer (EOC). Adipocyte derived seem to promote (EOC) growth progression by acting as mitochondrial fuel source support energy requirements EOC cells. Apart from a source, FFA may also enhance tumor through other signaling pathways that can proliferation regulate metabolism. Recently, family activated G-protein coupled receptors (FFAR/GPCRs) was identified, including: FFAR1/GPR40, FFAR2/GPR42, FFAR3/GPR41, FFAR4/GPR120 GPR84. Using RT-PCR, we found exposing cells adipocytes results in overexpression FFAR1/GPR40 multiple cell lines (ID8, A2780, C200, OVCAR3 SKOV3). In mRNA extracted formalin-fixed paraffin embedded specimens, approximately 80% high-grade serous carcinomas exhibited increased FFAR1 expression. Additionally, analysis TCGA database patients with tumors exhibiting expression had poor overall survival survival. We targeting using its specific antagonist GW1100 inhibited ID8, SKOV3 resulted downstream inhibition insulin secretion Akt pathway. On hand, treatment same agonist ,CAY10587, no effect on proliferation. Thus, conclude play important role regulation mediated Targeting be attractive strategy EOC, particularly for presenting high adiposity. Citation Format: Adnan Munkarah, Suhail Hamid, Jasdeep Chhina, Ismail Mert, LaToya Jackson, Sharon Hensley-Alford, Dhananjay Chitale, Shailendra Giri, Ramandeep Rattan. acid serve potential therapeutic approach. [abstract]. In: Proceedings AACR Special Conference Advances Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Res 2016;22(2 Suppl):Abstract nr A81.