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The Role Of Bca2 In Regulation Of Warburg-Like Glucose And Lactate Metabolism In Breast Cancer Cell Lines, Richard T. Arkwright Iii
The Role Of Bca2 In Regulation Of Warburg-Like Glucose And Lactate Metabolism In Breast Cancer Cell Lines, Richard T. Arkwright Iii
Wayne State University Dissertations
Modified metabolism is a hallmark of cancer cell biology known as “The Warburg Effect,” characterized by increased glucose-consumption and lactate-production, providing the metabolites and energy necessary for rapid proliferation. Breast-cancer-associated-gene-2 (BCA2) is an E3-Ub-ligase known to modulate AMPK, the “master-regulator of energy-homeostasis.” BCA2 is an oncogene associated with poor patient-survival and breast cancer invasiveness. Phospho-proteomic analysis of siBCA2-MDA-MB-231 knockdown-(KD) revealed enrichment of Nicotinamide-Nucleotide-Adenylyl-transferase-1 (NMNAT1), an essential enzyme in nuclear NAD-synthesis and a tumor-suppressor.
Initial experiments demonstrated that glucose concentration was positively correlated with BCA2 and inversely with NMNAT1 protein expression. shBCA2-KD in MDA-MB-468/-231 reproduced the inverse correlation between BCA2 and …