Arcangeli Annarosa
Department of Experimental Pathology and Oncology, University of Firenze, Viale Morgagni 50, 50134 Firenze, Italy.
Novartis Found Symp. 2005;266:225-32; discussion 232-4.
Increasing evidence indicates that ion channels are involved in the pathophysiology of cancer. The human ether-á-go-go-related gene (hERG) can be considered one of the most critical ion-channel encoding genes involved in the establishment and maintenance of neoplastic growth. In this review, evidence is presented to demonstrate that hERG channels are frequently over- and/or mis-expressed in many tumour cell lines as well as in primary human cancers. Moreover, many tumour cells, especially leukaemia cells, express a truncated isoform (hERG1B) along with the full length hERG1 protein, to form heterotetrameric channels. Three main functions relevant to tumour cell biology can be ascribed to hERG channel activity: (i) the control of cell proliferation, especially in leukaemias; (ii) the regulation of tumour cell invasiveness, possible through a physical and functional interaction with adhesion receptors of the integrin family; and (iii) the control of tumour cell neoangiogensis, through the modulation of angiogenic factor secretion. hERG channels are thus considered novel diagnostic and prognostic factors in human cancers, as well as targets for anti-neoplastic therapies.
越来越多的证据表明，离子通道参与了癌症的病理生理学过程。人类醚 - 去极化相关基因（hERG）可被视为参与肿瘤生长建立和维持的最关键的离子通道编码基因之一。在本综述中，有证据表明hERG通道在许多肿瘤细胞系以及原发性人类癌症中经常过度表达和/或错误表达。此外，许多肿瘤细胞，尤其是白血病细胞，除了全长hERG1蛋白外，还表达一种截短的异构体（hERG1B），以形成异源四聚体通道。hERG通道活性与肿瘤细胞生物学相关的三个主要功能如下：（i）控制细胞增殖，尤其是在白血病中；（ii）调节肿瘤细胞侵袭性，可能是通过与整合素家族的黏附受体进行物理和功能相互作用；（iii）通过调节血管生成因子的分泌来控制肿瘤细胞新生血管生成。因此，hERG通道被认为是人类癌症中新的诊断和预后因素，以及抗肿瘤治疗的靶点。
