Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells.

Mutations in calmodulin-binding domains of TRPV4/6 channels confer invasive properties to colon adenocarcinoma cells. Channels (Austin). 2020 Dec;14(1):101-109 Authors: Arbabian A, Iftinca M, Altier C, Singh PP, Isambert H, Coscoy S Abstract Transient receptor potential (TRP) channels form a family of polymodal cation channels gated by thermal, mechanical, or chemical stimuli, with many of them involved in the control of proliferation, apoptosis, or cell cycle. From an evolutionary point of view, TRP family is characterized by high conservation of duplicated genes originating from whole-genome duplication at the onset of vertebrates. The conservation of such "ohnolog" genes is theoretically linked to an increased probability of generating phenotypes deleterious for the organism upon gene mutation. We aimed to test experimentally the hypothesis that TRP mutations, in particular gain-of-function, could be involved in the generation of deleterious phenotypes involved in cancer, such as gain of invasiveness. Indeed, a number of TRP channels have been linked to cancer progression, and exhibit changes in expression levels in various types of cancers. However, TRP mutations in cancer have been poorly documented. We focused on 2 TRPV family members, TRPV4 and TRPV6, and studied the effect of putative gain-of-function mutations on invasiveness properties. TRPV channels have a C-terminal calmodulin-binding domain (CaMBD) that has important fun...
Source: Channels - Category: Molecular Biology Tags: Channels (Austin) Source Type: research