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Carbonic Anhydrase IX: Regulation and Role in Cancer

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Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications

Part of the book series: Subcellular Biochemistry ((SCBI,volume 75))

Abstract

Tumor microenvironment substantially influences the process of tumorigenesis. In many solid tumors, imbalance between the demand of rapidly proliferating cancer cells and the capabilities of the vascular system generates areas with insufficient oxygen supply. In response to tumor hypoxia, cancer cells modulate their gene expression pattern to match the requirements of the altered microenvironment. One of the most significant adaptations to this milieu is the shift towards anaerobic glycolysis to keep up the energy demands. This oncogenic metabolism is often maintained also in aerobic cells. Lactic acid, its metabolic end-product, accumulates hand-in-hand with carbon dioxide, leading to acidification of the extracellular environment. Carbonic anhydrase IX (CA IX) is the most widely expressed gene in response to hypoxia. Its crucial role in intracellular pH maintenance represents the means by which cancer cells adapt to the toxic conditions of the extracellular milieu. Furthermore, the activity of CA IX stimulates the migratory pathways of cancer cells and is connected with the increase of the aggressive/invasive phenotype of tumors. CA IX expression in many types of tumors indicates its relevance as a general marker of tumor hypoxia. Moreover, its expression is closely related to prognosis of the clinical outcome in several tumor types. All above mentioned facts support the strong position of CA IX as a potential drug therapy target. Here, we summarize the state-of-the-art knowledge on its regulation and role in cancer development.

Susan C. Frost and Robert McKenna (eds.) Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications

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Acknowledgments

The authors’ research is supported by grants from the 7th Framework program of EU (Collaborative project METOXIA), from the Research and Development Support Agency (DO7RP-0017-09, APVV-0893-11 and APVV-0658-11) and from the Research and Development Operational Program funded by the ERDF (project ITMS 26240120027).

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  1. Department of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovakia

    Martin Benej, Silvia Pastorekova & Jaromir Pastorek

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  1. Martin Benej
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  2. Silvia Pastorekova
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Correspondence to Jaromir Pastorek .

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  1. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA

    Susan C. Frost

  2. Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, Florida, USA

    Robert McKenna

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Benej, M., Pastorekova, S., Pastorek, J. (2014). Carbonic Anhydrase IX: Regulation and Role in Cancer. In: Frost, S., McKenna, R. (eds) Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications. Subcellular Biochemistry, vol 75. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7359-2_11

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