Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

Muhammad Yasir Asghar,Kid Törnquist

doi:10.3390/ijms21051739

Abstract

Calcium (Ca2+) is perhaps the most versatile signaling molecule in cells. Ca2+ regulates a large number of key events in cells, ranging from gene transcription, motility, and contraction, to energy production and channel gating. To accomplish all these different functions, a multitude of channels, pumps, and transporters are necessary. A group of channels participating in these processes is the transient receptor potential (TRP) family of cation channels. These channels are divided into 29 subfamilies, and are differentially expressed in man, rodents, worms, and flies. One of these subfamilies is the transient receptor potential canonical (TRPC) family of channels. This ion channel family comprises of seven isoforms, labeled TRPC1–7. In man, six functional forms are expressed (TRPC1, TRPC3–7), whereas TRPC2 is a pseudogene; thus, not functionally expressed. In this review, we will describe the importance of the TRPC channels and their interacting molecular partners in the etiology of cancer, particularly in regard to regulating migration and invasion.

Highlights

Increasing evidence during the past decade indicates that different ion channels are expressed in several cancers in humans, and regulate a multitude of cellular processes, including migration, invasion and proliferation [1,2,3]
Several transient receptor potential canonical (TRPC) channels are involved in regulating migration and invasion, and all are involved in enhancing proliferation of cancer cells [84,85,86]
We have shown that TRPC1 is a potent regulator of both migration and invasion in follicular thyroid cancer ML-1 cells [91]

Summary

Introduction

Increasing evidence during the past decade indicates that different ion channels are expressed in several cancers in humans, and regulate a multitude of cellular processes, including migration, invasion and proliferation [1,2,3]. Different Ca2+ channels gate Ca2+ ions into the cell, where after Ca2+ bind to Ca2+ binding proteins and activate downstream signaling pathways, resulting in specific cellular responses. These include motility and contraction, energy production, and gene transcription. The TRPC subfamily comprises six members in humans, TRPC1 and TRPC3–7 Many of these channels are ubiquitously expressed in human tissues and modulate a multitude of cellular responses [7,8,9,10,11,12]. Comprehensive overview of the importance of different ion channels, and not exclusively TRPC channels, see [2,3]

Calcium Signaling

TRPC Channels as Regulators of Migration and Invasion

TRPC Channels and Angiogenesis

Conclusions