cytoskeleton reorganization as an alternative mechanism of store-operated calcium entry control in neuroendocrine-differentiated cells细胞骨架重组作为门店的替代机制控制neuroendocrine-differentiated细胞钙条目.pdf

Cytoskeleton Reorganization as an Alternative Mechanism of Store-Operated Calcium Entry Control in Neuroendocrine-Differentiated Cells 1,2. 1,2. ´ ´ 1,2. ¨ 1,2. Karine Vanoverberghe , V’yacheslav Lehen’kyi , Stephanie Thebault , Maylis Raphael , Fabien Vanden Abeele1,2, Christian Slomianny1,2, Pascal Mariot1,2, Natalia Prevarskaya1,2* ´ 1 Inserm, U-1003, Equipe labellisee par la Ligue Nationale contre le cancer, Villeneuve d’Ascq, France, 2 Laboratory of Excellence, Ion Channels Science and Therapeutics, ´ Universite des Sciences et Technologies de Lille (USTL), Villeneuve d’Ascq, France Abstract Neuroendocrine differentiation (NED) is a hallmark of advanced androgen-independent prostate cancer, for which no successful therapy exists. NED tumour cells escape apoptotic cell death by alterations of Ca2+ homeostasis where the store- operated Ca2+ entry (SOCE) is known to be a key event. We have previously shown that the downregulation of Orai1 protein representing the major molecular component of endogenous SOCE in human prostate cancer cells, and constituting the principal source of Ca2+ influx used by the cell to trigger apoptosis, contributes to the establishment of an apoptosis- resistant phenotype (Cell Death Dis. 2010 Sep 16;1:e75.). Here, we report for the first time that the decrease of SOCE during NED may be caused by alternative NED-induced mechanism involving cytoskeleton reorganisation. NED induced by androgen deprivation resulted in a decrease of SOCE due to cortical F-actin over-polymerization which inhib