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

• DOI: 10.18632/oncotarget.8786
• Publication Date: 2016-04-19T04:24:38Z
• Authors: Maxime Guéguinou; Thomas Harnois; David Crottes; Arnaud Uguen; Nadine Deliot; Audrey Gambade; Aurélie Chantôme; 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-Cart...
• Keywords: 0301 basic medicine; ORAI1 Protein; Small-Conductance Calcium-Activated Potassium Channels; Immunoblotting; 610; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; anti-EGFR mAbs; lipid-raft channel complex; 03 medical and health sciences; Membrane Microdomains; [SDV.CAN] Life Sciences [q-bio]/Cancer; Cell Movement; Ohmline; [CHIM] Chemical Sciences; Akt signaling; Potassium Channel Blockers; [CHIM]Chemical Sciences; Humans; [SDV.BC] Life Sciences [q-bio]/Cellular Biology; TRPC Cation Channels; Antibodies, Monoclonal; HCT116 Cells; 3. Good health; ErbB Receptors; Multiprotein Complexes; Colonic Neoplasms; Calcium; Glycolipids; Proto-Oncogene Proteins c-akt; SOCE; Research Paper; Signal Transduction

// Maxime Guéguinou 1, 9 , Thomas Harnois 2, David Crottes 3 Arnaud Uguen 6, 7 Nadine Deliot Audrey Gambade 1 Aurélie Chantôme Jean Pierre Haelters 4, Paul Alain Jaffrès Marie Lise Jourdan 10 Günther Weber Olivier Soriani 8 Philippe Bougnoux 9, Mignen Nicolas Bourmeyster Bruno Constantin Thierry Lecomte 5, Christophe Vandier * Potier-Cartereau INSERM UMR 1069, Université de Tours, France 2 Equipe ERL 7368, CNRS, Poitiers, Department of Physiology, University California, San Francisco, CA, USA 4 CNRS-UMR 6521-Université Brest, 5 GICC-UMR 7292 6 INSERM-UMR 1078 CHRU Service d'Anatomie et Cytologie Pathologiques, CNRS 7299, 1099, Nice Sophia-Antipolis, Nice, Ion Channels Network and Cancer-Cancéropôle Grand Ouest (IC-CGO), These authors have contributed equally to this work Correspondence to: Potier-Cartereau, email: [e-mail] Keywords: SOCE, Ohmline, lipid-raft channel complex, anti-EGFR mAbs, Akt signaling Received: September 24, 2015 Accepted: March 28, 2016 Published: April 18, ABSTRACT Background: Barely 10-20% patients with metastatic colorectal cancer (mCRC) receive a clinical benefit from the use monoclonal antibodies (mAbs). We hypothesized that could depends on their efficiency reduce Store Operated Calcium Entry (SOCE) are known enhance cells. Results: In present study, we demonstrate SOCE promotes migration colon cell following formation lipid raft ion complex composed TRPC1/Orai1 SK3 channels. Formation is stimulated by phosphorylation reticular protein STIM1 EGF activation pathway. Our data show that, in positive feedback loop activates both pathway activity which lead amplification. This amplification occurs through Rac1/Calpain mediated Akt. also Anti-EGFR mAbs can modulate Interestingly, alkyl-lipid previously showed be an inhibitor channel, dissociated decreased modulation action. Conclusions: study demonstrates inhibition SOCE-dependent trough SK3/TRPC1/Orai1 Ohmline may novel strategy mAb action mCRC.