Girault Alban, Peretti Marta, Badaoui Mehdi, Hémon Anaïs, Morjani Hamid, Ouadid-Ahidouch Halima
Laboratory of Cellular and Molecular Physiology, UR UPJV 4667, University of Picardie Jules Verne Amiens, France.
Department of Cell Physiology & Metabolism, University of Geneva, Faculty of Medicine Geneva, Switzerland.
Am J Cancer Res. 2021 Jan 1;11(1):251-263. eCollection 2021.
It's now clearly established that the tumor microenvironment participates to tumor development. Among the different actors contributing to these processes, ion channels, located at the cancer cell surface, play a major role. We recently demonstrated that the association of Kv10.1, Orai1 and SPCA2 is crucial to promote the collagen-induced survival of MCF-7 breast cancer cells. By using siRNA directed against SPCA2, we shown that this protein is involved in the regulation of the activity, the expression and the sub-cellular localization of Kv10.1. In addition, it has been demonstrated that SPCA2 is involved in SICE in MCF-7 cells and that the N- and the C-terminal parts of this protein are necessary to interact and to produce Ca entry. However, no information is available about the necessary SPCA2's important region to regulate Kv10.1. The aim of our work is to evaluate how SPCA2 could interact with Kv10.1 channel to induce survival promotion. By using different SPCA2 mutants, we evaluate the role of the N- and C-terminal sections on the expression and the activity of Kv10.1 channels. In addition, we analyzed the impact of these deletions on the collagen 1-induced cell survival. Our results bring out new information about the regulation of Kv10.1 channel through SPCA2. More specifically how the N- and C-terminus of this Ca transporter regulate Kv10.1 expression, trafficking, and function suggesting new opportunities to target Kv10.1 channels in cancer progression.
现已明确肿瘤微环境参与肿瘤发展。在促成这些过程的不同因素中，位于癌细胞表面的离子通道起着主要作用。我们最近证明，Kv10.1、Orai1和SPCA2的关联对于促进MCF - 7乳腺癌细胞的胶原诱导存活至关重要。通过使用针对SPCA2的小干扰RNA（siRNA），我们表明该蛋白参与Kv10.1活性、表达及亚细胞定位的调节。此外，已证明SPCA2参与MCF - 7细胞中的SICE，且该蛋白的N端和C端对于相互作用及产生钙离子内流是必需的。然而，关于SPCA2调节Kv10.1所需的重要区域尚无信息。我们工作的目的是评估SPCA2如何与Kv10.1通道相互作用以促进存活。通过使用不同的SPCA2突变体，我们评估N端和C端部分对Kv10.1通道表达和活性的作用。此外，我们分析了这些缺失对胶原1诱导的细胞存活的影响。我们的结果揭示了关于通过SPCA2调节Kv10.1通道的新信息。更具体地说，这种钙转运蛋白的N端和C端如何调节Kv10.1的表达、运输和功能，这为在癌症进展中靶向Kv10.1通道提供了新的机会。
