Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Semin Cancer Biol. 2022 Nov;86(Pt 3):899-913. doi: 10.1016/j.semcancer.2022.01.001. Epub 2022 Jan 5.
The primary physiological process of respiration produces carbon dioxide (CO) that reacts with water molecules which subsequently liberates bicarbonate (HCO-) 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 overexpression of membrane-bound carbonic anhydrase IX (CAIX) is associated explicitly with hypoxic tumors or various solid cancers. CAIX helps tumors deal with higher CO 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 heterogeneity, 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, heterogeneity, and its structural insight to develop future combinatorial targeted cancer therapies.
呼吸的主要生理过程会产生二氧化碳（CO），CO 与水分子反应，随后释放出碳酸氢盐（HCO-）和质子。碳酸酐酶（CA）是参与这种转化的主要催化剂。人类 CA 有超过 16 种同工酶，表现出器官或亚细胞特异性活性。每种 CA 的失调都与多种病理有关。在这些成员中，膜结合碳酸酐酶 IX（CAIX）的过表达与缺氧肿瘤或各种实体癌明确相关。CAIX 通过与碳酸氢根离子结合将其隔离来帮助肿瘤应对更高水平的 CO，并帮助癌细胞在相对缺氧或酸性的环境中生长，从而充当 pH 适应开关。CAIX 介导的癌细胞适应性包括血管生成、代谢改变、肿瘤异质性、耐药性以及调节癌症特异性趋化因子。这篇综述全面收集并描述了 CAIX 在癌症生长、进展、异质性中的癌症特异性表达机制和作用，以及其结构见解，以开发未来的组合靶向癌症治疗方法。
