Yang Hanyu, Chen Rui, Zheng Xiang, Luo Yufan, Yao Mingxuan, Ke Famin, Guo Xiurong, Liu Xiaoyan, Liu Qiuyu
School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Department of Clinical Medicine, School of Clinical Medicine, Southwest Medical University, Luzhou 646000, China.
Cells. 2025 May 11;14(10):693. doi: 10.3390/cells14100693.
Cancer invasion and metastasis are critical factors that influence patient prognosis. Carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) are key regulators of hypoxia and pH homeostasis in the tumor microenvironment (TME). It has been verified that both CA IX and CA XII play significant roles in promoting tumor metastasis in recent years, but most of the literature tends to treat them as separate entities rather than exploring their synergistic effects. This review provides a comprehensive overview of the roles of CA IX and CA XII in tumor invasion and metastasis, along with their clinical applications, including their spatial distribution characteristics, molecular mechanisms that facilitate tumor metastasis, and their potential for clinical translation. Moreover, this review incorporates the classical tumor core-invasive front model to propose a metabolic coupling model of CA IX and CA XII, offering a fresh perspective on precision therapies that target tumor metabolism. By emphasizing the metabolic coupling between these two molecules, this review offers new insights distinct from previous studies and highlights the clinical therapeutic potential of simultaneously targeting both during treatment. It sheds new light on future research and clinical applications, aiming to enhance the prognosis of cancer patients through innovative therapeutic strategies.
癌症侵袭和转移是影响患者预后的关键因素。碳酸酐酶IX（CA IX）和碳酸酐酶XII（CA XII）是肿瘤微环境（TME）中缺氧和pH稳态的关键调节因子。近年来已证实，CA IX和CA XII在促进肿瘤转移方面均发挥着重要作用，但大多数文献倾向于将它们视为独立的实体，而非探讨它们的协同作用。本综述全面概述了CA IX和CA XII在肿瘤侵袭和转移中的作用及其临床应用，包括它们的空间分布特征、促进肿瘤转移的分子机制以及它们的临床转化潜力。此外，本综述结合经典的肿瘤核心侵袭前沿模型，提出了CA IX和CA XII的代谢偶联模型，为针对肿瘤代谢的精准治疗提供了新的视角。通过强调这两种分子之间的代谢偶联，本综述提供了与以往研究不同的新见解，并突出了在治疗过程中同时靶向两者的临床治疗潜力。它为未来的研究和临床应用提供了新的思路，旨在通过创新的治疗策略改善癌症患者的预后。
