Title:Recent Advances in Oncogenic Roles of the TRPM7 Chanzyme
Volume: 23
Issue: 36
Author(s): Mathieu Gautier, Marianne Perrière, Michael Monet, Alison Vanlaeys, Irina Korichneva, Isabelle Dhennin-Duthille and Halima Ouadid-Ahidouch
Affiliation:
Keywords:
TRPM7, epithelial cancer, calcium, magnesium, kinase, pharmacological blockers.
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.
