Recent Advances in Oncogenic Roles of the TRPM7 Chanzyme.

Abstract:

:Transient Receptor Potential Melastatin-related 7 (TRPM7) is a non-selective cation channel fused with a functional kinase domain. Physiologically, TRPM7 channel is involved in magnesium homeostasis, cell survival and gastrulation. The channel part is responsible for calcium, magnesium, and metal trace entries. Cation current through TRPM7 channel is inhibited by both intracellular magnesium and magnesium complexed with nucleotides. In parallel, the kinase is able to phosphorylate cytoskeleton proteins like myosin chain regulating cell tension and motility. Moreover, TRPM7 kinase domain can be cleaved by caspase and participates to apoptosis signaling. Importantly, TRPM7 channel expression is aberrant in numerous cancers including breast, glioblastoma, nasopharynx, ovarian, and pancreatic. Moreover, TRPM7 high expression is an independent biomarker of poor outcome in breast cancer. Pharmacological modulation or silencing of TRPM7 strongly affects proliferation, adhesion, migration or invasion in cancer cell lines. Nevertheless, it is still not clear by which mechanism TRPM7 channels may disturb cancer cell hallmarks. In the present review, we will discuss the role of TRPM7 channels in malignancies. In particular, we will distinguish the role of cation signaling from kinase function in order to better understand how TRPM7 channels may play a central role in cancer progression. We will also discuss the recent advances in pharmacological blockers of TRPM7 and their potential use for cancer therapy.

journal_name

Curr Med Chem

authors

Gautier M,Perrière M,Monet M,Vanlaeys A,Korichneva I,Dhennin-Duthille I,Ouadid-Ahidouch H

doi

10.2174/0929867323666160907162002

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

4092-4107

issue

36

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-78276

journal_volume

23

pub_type

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