Academic Journal
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
| العنوان: | 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 |
|---|---|
| المؤلفون: | Guéguinou, Maxime, Harnois, Thomas, Crottes, David, Uguen, Arnaud, Déliot, Nadine, Gambade, Audrey, Chantôme, Aurélie, Pierre Haelters, Jean, Jaffres, Paul-Alain, Lise Jourdan, Marie, Weber, Gunther, Soriani, Olivier, Bougnoux, Philippe, Mignen, Olivier, Bourmeyster, Nicolas, Lecomte, Thierry, Constantin, Bruno, Vandier, Christophe, Potier-Cartereau, Marie |
| المساهمون: | Network “Ion channels and Cancer-Canceropole Grand Ouest”, Cancéropôle Grand-Ouest, Niche, Nutrition, Cancer et métabolisme oxydatif (N2Cox), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Signalisation et Transports Ioniques Membranaires (STIM Poitiers ), Université de Poitiers = University of Poitiers (UP)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), University of California San Francisco (UC San Francisco), University of California (UC), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), CHU Trousseau Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS 2012-2017 (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 1949-2553 ; Oncotarget ; https://hal.univ-brest.fr/hal-01539569 ; Oncotarget, 2016, 7, pp.36168-36184. ⟨10.18632/oncotarget.8786⟩ ; http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=8786&path[]=26521. |
| بيانات النشر: | CCSD Impact journals |
| سنة النشر: | 2016 |
| المجموعة: | Université de Bretagne Occidentale: HAL |
| مصطلحات موضوعية: | anti-EGFR mAbs, lipid-raft channel complex, Ohmline, Akt signaling, SOCE, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [CHIM]Chemical Sciences, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; Background: 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.Results: 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.Conclusions: 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | PUBMEDCENTRAL: PMC5094991 |
| DOI: | 10.18632/oncotarget.8786 |
| الاتاحة: | https://hal.univ-brest.fr/hal-01539569 https://doi.org/10.18632/oncotarget.8786 |
| رقم الانضمام: | edsbas.55F3613 |
| قاعدة البيانات: | BASE |
| DOI: | 10.18632/oncotarget.8786 |
|---|