Abstract

“Moonlighting Functions” of Glycolytic Enzymes as Emerging Targets for Preventing Cancer Cell Invasion and Metastasis

Hirak Basu, Associate Professor, University of Texas MD Anderson Cancer Center

Metastatic castration-resistant prostate cancer is the second leading cause of cancer deaths in US men. Metabolic oxidative stress is involved in all stages of prostate cancer occurrence, recurrence as well as its progression to its often fatal castration-resistant state. We have reported that an activation of a specificmetabolic pathway of polyamine oxidation as a major source of oxidative stress generation in polyamine-rich prostate cancer cells. We have also shown that this pathway is involved in setting up an autocrine feed-forward loop that supports the proliferation of androgen dependent prostate cancer cells to proliferate in the absence of androgen (castration-resistance). Our recent unpublished data show that oxidation of certain glycolytic enzymes leads to a loss of their glycolytic function and increases their “Moonlighting Functions” related to actin polymerization leading to cell invasion and metastasis.Oxidative modifications of mitochondria also have profound effect on cellular autophagy that imparts resistance to anti-androgen-induced apoptosis. Novel therapeutic agents targeting oxidative modifications targeting prostate cancer cells developed in our laboratory showed profound effect in arresting castration-resistant human prostate cancer cell growth both in culture as well as in animal xenograft models. These agents are currently undergoing preclinical development for clinical trials in the near future.