Channelpedia

PubMed 27102434


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: SK3 , TRP , TRPC , TRPC1



Title: SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline.

Authors: Maxime Guéguinou, Thomas Harnois, David Crottes, Arnaud Uguen, Nadine Déliot, Audrey Gambade, Aurelie Chantome, Jean Pierre Haelters, Paul Alain Jaffrès, Marie Lise Jourdan, Günther Weber, Olivier Soriani, Philippe Bougnoux, Olivier Mignen, Nicolas Bourmeyster, Bruno Constantin, Thierry Lecomte, Christophe Vandier, Marie Potier-Cartereau

Journal, date & volume: Oncotarget, 2016 Apr 18 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/27102434


Abstract
Barely 10-20% of patients with metastatic colorectal cancer (mCRC) receive a clinical benefit from the use of anti-EGFR monoclonal antibodies (mAbs). We hypothesized that this could depends on their efficiency to reduce Store Operated Calcium Entry (SOCE) that are known to enhance cancer cells.In the present study, we demonstrate that SOCE promotes migration of colon cancer cell following the formation of a lipid raft ion channel complex composed of TRPC1/Orai1 and SK3 channels. Formation of this complex is stimulated by the phosphorylation of the reticular protein STIM1 by EGF and activation of the Akt pathway. Our data show that, in a positive feedback loop SOCE activates both Akt pathway and SK3 channel activity which lead to SOCE amplification. This amplification occurs through the activation of Rac1/Calpain mediated by Akt. We also show that Anti-EGFR mAbs can modulate SOCE and cancer cell migration through the Akt pathway. Interestingly, the alkyl-lipid Ohmline, which we previously showed to be an inhibitor of SK3 channel, can dissociated the lipid raft ion channel complex through decreased phosphorylation of Akt and modulation of mAbs action.This study demonstrates that the inhibition of the SOCE-dependent colon cancer cell migration trough SK3/TRPC1/Orai1 channel complex by the alkyl-lipid Ohmline may be a novel strategy to modulate Anti-EGFR mAb action in mCRC.