Carbonic Anhydrase IX: Regulation and Role in Cancer
Carbonic Anhydrase IX: Regulation and Role in Cancer
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DOI：
10.1007/978-94-007-7359-2_11
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发表时间：
2014-01-01
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影响因子：
--
通讯作者：
Pastorek, Jaromir
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文献类型：
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作者：
Benej, Martin;Pastorekova, Silvia;Pastorek, Jaromir
肿瘤微环境在很大程度上影响着肿瘤的发生过程。在许多实体瘤中，快速增殖的癌细胞的需求与血管系统的能力之间的不平衡产生氧气供应不足的区域。为了响应肿瘤缺氧，癌细胞调节其基因表达模式以匹配改变的微环境的要求。对这种环境的最重要的适应之一是转向无氧糖酵解以保持能量需求。这种致癌代谢通常也维持在需氧细胞中。其代谢终产物乳酸与二氧化碳一起积累，导致细胞外环境酸化。碳酸酐酶IX（CA IX）是缺氧反应中表达最广泛的基因。其在细胞内pH维持中的关键作用代表了癌细胞适应细胞外环境的毒性条件的手段。此外，CA IX的活性刺激癌细胞的迁移途径，并与肿瘤的侵袭性/侵袭性表型的增加有关。CA IX在许多类型的肿瘤中的表达表明其作为肿瘤缺氧的一般标志物的相关性。此外，它的表达与几种肿瘤类型的临床结果的预后密切相关。所有上述事实支持CA IX作为潜在药物治疗靶点的强有力地位。在这里，我们总结了其在癌症发展中的调节和作用的最新知识。
Tumor microenvironment substantially influences the process of tumorigenesis. In many solid tumors, imbalance between the demand of rapidly proliferating cancer cells and the capabilities of the vascular system generates areas with insufficient oxygen supply. In response to tumor hypoxia, cancer cells modulate their gene expression pattern to match the requirements of the altered microenvironment. One of the most significant adaptations to this milieu is the shift towards anaerobic glycolysis to keep up the energy demands. This oncogenic metabolism is often maintained also in aerobic cells. Lactic acid, its metabolic end-product, accumulates hand-in-hand with carbon dioxide, leading to acidification of the extracellular environment. Carbonic anhydrase IX (CA IX) is the most widely expressed gene in response to hypoxia. Its crucial role in intracellular pH maintenance represents the means by which cancer cells adapt to the toxic conditions of the extracellular milieu. Furthermore, the activity of CA IX stimulates the migratory pathways of cancer cells and is connected with the increase of the aggressive/invasive phenotype of tumors. CA IX expression in many types of tumors indicates its relevance as a general marker of tumor hypoxia. Moreover, its expression is closely related to prognosis of the clinical outcome in several tumor types. All above mentioned facts support the strong position of CA IX as a potential drug therapy target. Here, we summarize the state-of-the-art knowledge on its regulation and role in cancer development.