Document Detail


Cytoskeleton reorganization as an alternative mechanism of store-operated calcium entry control in neuroendocrine-differentiated cells.
MedLine Citation:
PMID:  23049826     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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 Ca(2+) homeostasis where the store-operated Ca(2+) 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 Ca(2+) 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 inhibits thapsigargin-induced SOCE. The disruption of F-actin polymerization by Cytochalasin D in NED cells restored SOCE, while the induction of F-actin polymerization by jasplakinolide or calyculin A diminished SOCE without changing the expression of key SOCE players: Orai1, STIM1, and TRPC1. Our data suggest that targeting cytoskeleton-induced pathways of malignant cells together with SOCE-involved channels may prove a useful strategy in the treatment of advanced prostate cancer.
Authors:
Karine Vanoverberghe; V'yacheslav Lehen'kyi; Stéphanie Thébault; Maylis Raphaël; Fabien Vanden Abeele; Christian Slomianny; Pascal Mariot; Natalia Prevarskaya
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Publication Detail:
Type:  Journal Article     Date:  2012-09-25
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45615     Citation Subset:  IM    
Affiliation:
Inserm, U-1003, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France ; Laboratory of Excellence, Ion Channels Science and Therapeutics, Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France.
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