Chinigò Giorgia, Fiorio Pla Alessandra, Gkika Dimitra
Laboratory of Cellular and Molecular Angiogenesis, Department of Life Sciences and Systems Biology, University of Torino, Torino, Italy.
Laboratoire de Cell Physiology, Université de Lille, Department of Life Sciences, Univ. Lille, Inserm, U1003-PHYCEL, Lille, France.
Front Pharmacol. 2020 Sep 29;11:581455. doi: 10.3389/fphar.2020.581455. eCollection 2020.
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 both Ca-dependent or Ca-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.
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可能涉及的多种途径中，我们在此将注意力集中于涉及小GTP酶（GTPases）的途径，总结与转移级联相关的主要过程，如迁移、侵袭和肿瘤血管生成。在过去十年中，多项研究强调了TRP与小GTP酶在癌症进展中的双向相互作用：TRP通道可能通过钙依赖或非钙依赖途径影响小GTP酶的活性，反之，一些小GTP酶可能通过调节TRP通道向质膜的细胞内转运或直接作用于通道门控来影响TRP通道的活性。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协同作用，以及TRPC1、TRPC6、TRPM8、TRPV4与Rho和Ras样GTP酶在诱导异常肿瘤血管生成中的相互作用。
