A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells.

A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells. Biochem J. 2019 May 09;: Authors: Mboge MY, Chen Z, Khokhar D, Wolff A, Ai L, Heldermon CD, Bozdag M, Carta F, Supuran CT, Brown KD, McKenna R, Frost CJ, Frost SC Abstract The most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production.  This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt.  We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression.  Yet, isoform selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation.  Other investigators have suggested the CA IX cooperates with the MCT transport family to excrete protons.  To test this possibility, we examined the express...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research