Insufficient oxygen supply, hypoxia, is one of the most typical phenomena characterizing a tumor microenvironment. A typical manifestation of adaptation to hypoxia is a metabolic shift from mitochondrial respiration to glycolysis and the formation of an acidic cell microenvironment [1]. Hypoxia and related acidosis disrupt normal physiologic functions and play a role in promoting the invasiveness, metastases, chemoresistance and immunoresistance in tumor cells [2, 3]. Adaptation to hypoxia and extracellular acidosis represent a crucial step for cell survival. The tumor cells express a wide range of genes whose products allow adaptation to these limiting factors [4]. One of them, carbonic anhydrase IX (CA IX) is a hypoxia-induced catalytically active enzyme which contributes to neutralization of the intracellular pH, and to acidification of the extracellular pH [5, 6]. In terms of contribution to the extracellular acidosis, CA IX is regarded as the active component of the prometastatic cascade, cell adhesion and cell migration [7]. The expression of CA IX is strongly associated with poor prognosis and the malignant phenotype. In this study, we present evidence of a novel relationship between CA IX and glycolysis and suggest that CA IX via its expression and catalytic activity cooperates with components of glycolytic metabolism. We believe that our results will contribute to a better understanding of the role of CA IX in cancer metabolism.
Financial support: Research and Development Support Agency (APVV-0658-11), 7th Framework program of EU (Collaborative project METOXIA), Slovak Scientific Grant Agency (VEGA 2/0130/11), Research and Development Operational Program funded by the ERDF (project ITMS 26240220062).
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