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Carbonic Anhydrase IX (CAIX) as a Mediator of Hypoxia-Induced Stress Response in Cancer Cells

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

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

Abstract

The development of hypoxic microenvironments within many types of solid tumors imposes a significant stress on cancer cells to which they must respond appropriately in order to survive and grow. Tumor-specific, hypoxia-induced upregulation of Carbonic Anhydrase IX (CAIX) is a component of the complex response of cancer cells to the evolving low oxygen environment. Here, we discuss evidence from in vivo tumor models employing inhibition or enhancement of CAIX expression, using gene depletion or overexpression strategies, respectively, or inhibition of its catalytic activity, using CAIX-specific small molecules or antibodies, to demonstrate that CAIX is a functional mediator of tumor growth and metastasis. We also discuss the functional contribution of CAIX to several specific biological processes critical for cancer progression, including pH regulation and cell survival, adhesion, migration and invasion, the maintenance of cancer stem cell function, and the acquisition of chemo and radioresistant properties. The demonstration of CAIX as a functional mediator of cancer progression provides a biological rationale for its use as a cancer-specific, clinically relevant therapeutic target.

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

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Author information

Authors and Affiliations

  1. Department of Integrative Oncology, British Columbia Cancer Agency Centre, Vancouver, BC, Canada

    Paul C. McDonald

  2. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada

    Shoukat Dedhar

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  1. Paul C. McDonald
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  2. Shoukat Dedhar
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Correspondence to Shoukat Dedhar .

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Editors and Affiliations

  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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McDonald, P.C., Dedhar, S. (2014). Carbonic Anhydrase IX (CAIX) as a Mediator of Hypoxia-Induced Stress Response in Cancer Cells. 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_13

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