Original association of ion transporters mediates the ECM-induced breast cancer cell survival: Kv10.1-Orai1-SPCA2 partnership.
Fiche publication
Date publication
février 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MORJANI Hamid
Tous les auteurs :
Peretti M, Badaoui M, Girault A, Van Gulick L, Mabille MP, Tebbakha R, Sevestre H, Morjani H, Ouadid-Ahidouch H
Lien Pubmed
Résumé
In the last years it has been shown that many components of tumor microenvironment (TM) can induce cell signaling that permit to breast cancer cells (BC) to maintain their aggressiveness. Ion channels have a role in mediating TM signal; recently we have demonstrated a functional collaboration between Kv10.1 and Orai1 channels in mediating the pro-survival effect of collagen 1 on BC cells. Here we show how SPCA2 (Secretory Pathway Ca ATPase) has a role in this process and is able to support survival and proliferation induced by collagen 1. By participating to an auto-sustaining loop, SPCA2 enhances membrane expression of Kv10.1 and Orai1; the activity of every component of this trio is necessary to mediate a store independent calcium entry (SICE). This SICE is fundamental to maintain both the activation of the pro-survival pathway and the membrane localization and consequently the activity of the two channels. Moreover, the three proteins and the collagen receptor DDR1 are overexpressed only in aggressive tumors tissues. In this work, we propose a novel association between SPCA2, Kv10.1 and Orai1 involved in mediating transduction signals from TM to the BC cells that can be potentially exploited in the search of novel therapeutic targets specific to tumor tissues.
Référence
Sci Rep. 2019 Feb 4;9(1):1175