HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

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

Maxime Guéguinou 1, 2 Thomas Harnois 3, 1 David Crottes 4 Arnaud Uguen 5, 6 Nadine Deliot 3, 1 Audrey Gambade 2 Aurélie Chantôme 2, 1 Jean Pierre Haelters 7, 1 Paul-Alain Jaffres 7 Marie Lise Jourdan 2, 8 Gunther Weber 2 Olivier Soriani 9 Philippe Bougnoux 2, 8, 1 Olivier Mignen 2, 1 Nicolas Bourmeyster 3, 1 Thierry Lecomte 10, 8, 1 Bruno Constantin 3, 1 Christophe Vandier 2, 1 Marie Potier-Cartereau 2, 1
1 Network “Ion channels and Cancer-Canceropole Grand Ouest”
2 N2C - Nutrition, croissance et cancer (U 1069)
3 STIM - Signalisation et Transports Ioniques Membranaires
4 UCSF - University of California [San Francisco]
5 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
6 Service d’Anatomie et Cytologie Pathologiques
7 CEMCA - Chimie, Electrochimie Moléculaires et Chimie Analytique
8 CHU Trousseau [Tours]
9 CNRS UMR 7277, INSERM-U1091
10 GICC UMR 7292 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017]
Abstract : 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.
Keywords : Akt signaling SOCE Ohmline lipid-raft channel complex anti-EGFR mAbs
Document type :
Journal articles
Complete list of metadata
https://hal.univ-brest.fr/hal-01539569
Contributor : Nicolas Renard Connect in order to contact the contributor
Submitted on : Thursday, June 15, 2017 - 10:01:38 AM
Last modification on : Thursday, March 3, 2022 - 4:44:02 PM

Links full text

pubmedcentral

Identifiers

Collections

UNIV-BREST | CNRS | UNIV-POITIERS | CEMCA-BREST | INC-CNRS | UNIV-TOURS | GGFB | IBSAM | UNIV-COTEDAZUR | INSERM | STIM

Citation

Maxime Guéguinou, Thomas Harnois, David Crottes, Arnaud Uguen, Nadine Deliot, et al.. 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. Oncotarget, Impact journals, 2016, 7, pp.36168-36184. ⟨10.18632/oncotarget.8786⟩. ⟨hal-01539569⟩

Export

BibTeX TEI DC DCterms EndNote Datacite

Share

Metrics

Record views

131