Hope Jacob M, Greenlee Joshua D, King Michael R
From the Department of Biomedical Engineering, Vanderbilt University, Nashville, TN.
Cancer J. 2018 Mar/Apr;24(2):84-92. doi: 10.1097/PPO.0000000000000312.
Cancer metastasis is the second leading cause of death in the United States. Despite its morbidity, metastasis is an inefficient process that few cells can survive. However, cancer cells can overcome these metastatic barriers via cellular responses to microenvironmental cues, such as through mechanotransduction. This review focuses on the mechanosensitive ion channels TRPV4 and P2X7, and their roles in metastasis, as both channels have been shown to significantly affect tumor cell dissemination. Upon activation, these channels help form tumor neovasculature, promote transendothelial migration, and increase cell motility. Conversely, they have also been linked to forms of cancer cell death dependent upon levels of activation, implying the complex functionality of mechanosensitive ion channels. Understanding the roles of TRPV4, P2X7 and other mechanosensitive ion channels in these processes may reveal new possible drug targets that modify channel function to reduce a tumor's metastatic potential.
癌症转移是美国第二大死因。尽管其发病率高,但转移是一个低效的过程,很少有细胞能够存活。然而,癌细胞可以通过对微环境线索的细胞反应来克服这些转移障碍,例如通过机械转导。本综述聚焦于机械敏感离子通道TRPV4和P2X7及其在转移中的作用,因为这两种通道均已显示出对肿瘤细胞扩散有显著影响。激活后,这些通道有助于形成肿瘤新生血管,促进跨内皮迁移,并增加细胞运动性。相反,它们也与取决于激活水平的癌细胞死亡形式有关,这意味着机械敏感离子通道具有复杂的功能。了解TRPV4、P2X7和其他机械敏感离子通道在这些过程中的作用,可能会揭示新的潜在药物靶点,通过改变通道功能来降低肿瘤的转移潜力。