TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer.

TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer.
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DOI:
10.3389/fphar.2020.581455
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发表时间:
2020
影响因子:
5.6
通讯作者:
Gkika D
Gkika D
中科院分区:
医学2区
文献类型:
--
作者:
Chinigò G;Fiorio Pla A;Gkika D

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瞬时受体电位 (TRP) 阳离子通道作为细胞内钙稳态的关键调节因子,在癌症的基本特征中发挥着核心作用。在TRP可能参与的多种途径中,我们重点关注涉及小鸟苷三磷酸酶(GTPase)的途径,总结了与转移级联相关的主要过程,例如迁移、侵袭和肿瘤血管化。在过去的十年中,一些研究强调了 TRP 和小 GTP 酶在癌症进展中的双向相互作用:TRP 通道可能通过 Ca2+ 依赖性或 Ca2+ 独立途径影响小 GTP 酶活性,相反,一些小 GTP 酶可能通过调节其细胞内运输到质膜或直接作用于通道门控来影响 TRP 通道活性。特别是,我们将描述 TRPC1、TRPC5、TRPC6、TRPM4、TRPM7 或 TRPV4 与 Rho 样 GTP 酶在调节细胞迁移中的相互作用,TRPM2 和 TRPV2 与 Rho GTP 酶在增加细胞侵袭性方面的合作,最后,TRPC1、TRPC6、TRPM8、TRPV4 与 Rho 和 Ras 样 GTP 酶在诱导异常肿瘤血管化中的串扰。
Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention on the ones involving small guanosine triphosphatases (GTPases), summarizing the main processes associated with the metastatic cascade, such as migration, invasion and tumor vascularization. In the last decade, several studies have highlighted a bidirectional interplay between TRPs and small GTPases in cancer progression: TRP channels may affect small GTPases activity via both Ca2+-dependent or Ca2+-independent pathways, and, conversely, some small GTPases may affect TRP channels activity through the regulation of their intracellular trafficking to the plasma membrane or acting directly on channel gating. In particular, we will describe the interplay between TRPC1, TRPC5, TRPC6, TRPM4, TRPM7 or TRPV4, and Rho-like GTPases in regulating cell migration, the cooperation of TRPM2 and TRPV2 with Rho GTPases in increasing cell invasiveness and finally, the crosstalk between TRPC1, TRPC6, TRPM8, TRPV4 and both Rho- and Ras-like GTPases in inducing aberrant tumor vascularization.
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