title: Carbonic anhydrase IX (CAIX) as a mediator of hypoxia-induced stress response in cancer cells.
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.
authors.affiliation: Department of Integrative Oncology, British Columbia Cancer Agency Centre, Vancouver, BC, Canada, pmcdonal@bccrc.ca.
authors.forename: Paul C
authors.initials: PC
authors.lastname: McDonald
authors.forename: Shoukat
authors.initials: S
authors.lastname: Dedhar
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D002245:Carbon Dioxide; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases