KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis.

Rivas J, Díaz N, Silva I, Morales D, Lavanderos B, Álvarez A, Saldías MP, Pulgar E, Cruz P, Maureira D, Flores G, Colombo A, Blanco C, Contreras HR, Jaña F, Gallegos I, Concha ML, Vergara-Jaque A, Poblete H, González W, Varela D, Trimmer JS, Cáceres M, Ce

Keywords: KCTD5, TRPM4, BREAST CANCER

Abstract

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+ -activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.

Más información

Título de la Revista: FASEB JOURNAL
Volumen: 34
Editorial: The Federation of American Societies for Experimental Biology
Fecha de publicación: 2020
Página de inicio: 7847
Página final: 7865
Idioma: Inglés
Financiamiento/Sponsor: FONDECYT 1160518; 1160900; 1181263
URL: https://pubmed.ncbi.nlm.nih.gov/32301552/
DOI:

doi: 10.1096/fj.201901195RRR

Notas: ISI, SCOPUS