Abstract 5100: Aerobic glycolysis is the primary metabolic pathway used for prostate cancer cell motility and invasion processes regardless of androgen sensitivity

Abstract

Abstract The ability of a cancer cell to detach from a primary tumor and intravasate is a fundamental prerequisite for development of metastatic disease. As metastatic tumors are frequently the principal cause of death in cancer patients with advanced disease, targeting the ability of cancer cells to metastasize may improve patient outcomes. Advanced, aggressive prostate cancers are characterized by abnormal metabolic upregulation of aerobic glycolysis, a phenomenon known as the Warburg effect. We have previously demonstrated that prostate cancer and breast cancer cells use aerobic glycolysis as the primary energy pathway for cellular motility and cytoskeletal remodeling. In clinical prostate cancer patients, the progression of cells to an androgen insensitive state renders treatment difficult and often unsuccessful. In the present study, we investigate the role of aerobic glycolysis in motility and invasion in prostate cancer cells with intact androgen signaling. To test this, we utilized a Seahorse XF24 metabolic to measure aerobic glycolysis and oxygen consumption rate of prostate cancer cells with and without intact androgen receptor signaling. Cellular motility was measured by tracking cell movement over time while subjecting cells to pharmacological inhibition of aerobic glycolysis, mitochondrial oxidative phosphorylation, or fatty acid beta-oxidation. Cellular invasion was measured by a Boyden chamber invasion assay with similar pharmacological inhibition. As anticipated, prostate cancer cells with intact androgen receptor signaling displayed a modulated usage of aerobic glycolysis, whereas mitochondrial oxidative phosphorylation was unchanged. Consequently, androgen receptor signaling altered cancer cell invasiveness. Notably, regardless of invasiveness and androgen receptor status, cellular motility and invasion capacity can be attenuated upon pharmacological inhibition of aerobic glycolysis. Taken together, these data suggest that targeting aerobic glycolysis in prostate cancer could severely weaken prostate cancer metastatic capability and limit tumor spread from the primary site. In the future, combining glycolytic inhibitors with conventional therapy may prevent dissemination of metastatic clones to distal sites and thus drastically reduce risk of metastatic recurrence. Citation Format: James E. Verdone, Jelani C. Zarif, Kenneth J. Pienta. Aerobic glycolysis is the primary metabolic pathway used for prostate cancer cell motility and invasion processes regardless of androgen sensitivity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5100. doi:10.1158/1538-7445.AM2015-5100