期刊
SEMINARS IN CANCER BIOLOGY
卷 86, 期 -, 页码 899-913出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2022.01.001
关键词
Carbonic anhydrases; Heterogeneity; Transport metabolon; Tumor hypoxia; Small molecule inhibitors; Isoform selectivity
类别
资金
- Council of Scientific and Industrial Research, India
- [27 (0368) /20-EMR-II]
This review comprehensively gathers and describes the cancer-specific expression mechanism and role of CAIX in cancer growth, progression, heterogeneity, and its structural insight for the development of future combinatorial targeted cancer therapies.
The primary physiological process of respiration produces carbon dioxide (CO2) that reacts with water molecules which subsequently liberates bicarbonate (HCO-3) and protons. Carbonic anhydrases (CAs) are the primary catalyst involved in this conversion. More than 16 isoforms of human CAs show organ or subcellular specific activity. Dysregulation of each CA is associated with multiple pathologies. Out of these members, the over -expression of membrane-bound carbonic anhydrase IX (CAIX) is associated explicitly with hypoxic tumors or various solid cancers. CAIX helps tumors deal with higher CO2 by sequestering it with bicarbonate ions and helping cancer cells to grow in a comparatively hypoxic or acidic environment, thus acting as a pH adaptation switch. CAIX-mediated adaptations in cancer cells include angiogenesis, metabolic alterations, tumor hetero-geneity, drug resistance, and regulation of cancer-specific chemokines. This review comprehensively collects and describe the cancer-specific expression mechanism and role of CAIX in cancer growth, progression, heteroge-neity, and its structural insight to develop future combinatorial targeted cancer therapies.
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