Endoplasmic reticulum Ca(2+) content decrease by PKA-dependent hyperphosphorylation of type 1 IP3 receptor contributes to prostate cancer cell resistance to androgen deprivation

Cell Calcium
Benoît BoutinPhilippe Gailly

Abstract

Reference treatment of advanced prostate cancer (PCa) relies on pharmacological or surgical androgen deprivation therapy. However, it is only temporarily efficient as tumor cells inevitably adapt to the low testosterone environment and become hormone-refractory (HRPCa). We observed that androgen removal in HRPCa-derived LNCaP cells causes different alterations in their Ca(2+) homeostasis among which a reduction of ER Ca(2+) content. We show that the decrease in [Ca(2+)]ER is due to a modest overexpression of type 1 IP3R and a threefold increased phosphorylation of IP3R1 on Ser-1716, a protein kinase A (PKA) consensus site, both implicated in ER Ca(2+) leak. Accordingly, ER Ca(2+) content was restored by siRNA-mediated down-regulation of IP3R1 or by inhibition of its phosphorylation by competition with a permeant TAT-peptide containing the Ser-1716 consensus phosphorylation sequence or by treatment with the PKA inhibitor H89. Moreover, inhibition of the IP3R1 phosphorylation by both methods sensitized the LNCaP cells to androgen deprivation-induced apoptosis. In addition, SERCA2b overexpression precluded the effect of androgen deprivation on ER Ca(2+) store content and reduced resistance to androgen deprivation. Taken together, ...Continue Reading

References

Jan 25, 2003·Cell Calcium·C CamelloA V Tepikin
Oct 1, 2003·The Prostate·Adrie van BokhovenM Scott Lucia
Dec 20, 2003·Cell Death and Differentiation·K VanoverbergheN Prevarskaya
Aug 3, 2004·Science·Douglas R Green, Guido Kroemer
Oct 8, 2004·The New England Journal of Medicine·Daniel P PetrylakE David Crawford
Dec 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott A OakesStanley J Korsmeyer
Sep 5, 2006·Cellular Signalling·Anne-Katrine KvisselKristin Austlid Taskén
Jan 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Dominik R BertholdIan F Tannock
Oct 16, 2008·Anti-cancer Agents in Medicinal Chemistry·A Bergner, R M Huber
Apr 25, 2009·The International Journal of Biochemistry & Cell Biology·Carlotta GiorgiPaolo Pinton
Nov 16, 2011·Autophagy·Jean-Paul DecuypereGeert Bultynck
Sep 12, 2012·Autophagy·Daniel J KlionskyBrian Zuckerbraun
Dec 13, 2012·Biochimica Et Biophysica Acta·Haidar Akl, Geert Bultynck
Jan 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ming-Jin ChangClark W Distelhorst

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Citations

Aug 12, 2016·Physiological Reviews·Michael J Berridge
Nov 16, 2019·Annual Review of Physiology·Kozo Hamada, Katsuhiko Mikoshiba
Mar 20, 2019·Cancers·Philippe KischelHalima Ouadid-Ahidouch
Apr 3, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Fernanda O LemosJan B Parys
Dec 22, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Perla Pérez-TreviñoNoemí García

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