Regulation of ion channels in cancer

Ion channels participate to virtually all cellular processes by initiating and shaping signaling pathways, and regulating cell osmolarity and morphology. Interestingly, ion channels are often aberrantly expressed in cancers and their initial functions are then hijacked to potentiate proliferation, insensitivity to antigrowth signals, evasion of programmed cell death (apoptosis), sustained angiogenesis, tissue invasion and metastasis. Moreover, ion channels are key players of the crosstalk between cancer cells and the tumor micro-environment, participating to the tumor tissue remodeling. Consequently, ion channels represent an unexplored class of targets for cancer therapy. Therefore, understanding the specific regulation of ion channels within the cancer tissue is a crucial challenge to develop alternative treatments.

Our group has focused his research on the Sigma1 receptor (Sig1R), a chaperone protein activated in response to cell stress conditions encountered within tumors such as hypoxia and nutrient deprivation. We have established that ion channels from different families are the main clients of Sig1R.Sig1R, regulates their activity through the control of their expression at the plasma membrane and further association with membrane receptors including integrins and growth factor receptors.

 

 

Our current investigations conducted in myeloid leukemia and pancreatic adenocarcinoma models, aim at understanding the role of Sig1R in the shaping of cancer cell electrical activity, and the consequences of Sig1R inhibition (either by molecular silencing or pharmacological inhibition using sigma ligands) on cancer cell behavior in vivo and in vitro. Our purpose is to propose small molecule sigma ligands to regulate Sig1R/ion channel complexes in order to reduce tumor cell invasiveness potency and chemotherapy resistance.

 

 

Last publications

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca(2+) homeostasis. - 2017 - Oncogene - Gueguinou M, Crottès D, Chantôme A, Rapetti-Mauss R, Potier-Cartereau M, Clarysse L, Girault A, Fourbon Y, Jézéquel P, Guérin-Charbonnel C, Fromont G, Martin P, Pellissier B, Schiappa R, Chamorey E, Mignen O, Uguen A, Borgese F, Vandier C, and Soriani,O

Sigma 1 Receptor and Ion Channel Dynamics in Cancer. - 2017 - Advances in experimental medicine and biology - 964 P63-77 - Soriani O, and Rapetti-Mauss,R

Immature human dendritic cells enhance their migration through KCa3.1 channel activation. - 2016 - Cell calcium - 59 P198-207 - Crottès D, Félix R, Meley D, Chadet S, Herr F, Audiger C, Soriani O, Vandier C, Roger S, Angoulvant D, and Velge-Roussel,F

Senicapoc: a potent candidate for the treatment of a subset of hereditary xerocytosis caused by mutations in the Gardos channel. - 2016 - Haematologica - 101 Pe431-e435 - Rapetti-Mauss R, Soriani O, Vinti H, Badens C, and Guizouarn,H

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. - 2016 - Oncotarget - 7 P36168-36184 - Guéguinou M, Harnois T, Crottes D, Uguen A, Deliot N, Gambade A, Chantôme A, Haelters JP, Jaffrès PA, Jourdan ML, Weber G, Soriani O, Bougnoux P, Mignen O, Bourmeyster N, Constantin B, Lecomte T, Vandier C, and Potier-Cartereau,M

SigmaR1 regulates membrane electrical activity in response to extracellular matrix stimulation to drive cancer cell invasiveness. - 2015 - Cancer research - Crottès D, Rapetti-Mauss R, Alcaraz-Perez F, Tichet M, Gariano G, Martial S, Guizouarn H, Pellissier B, Loubat A, Popa A, Paquet A, Presta M, Tartare-Deckert S, Cayuela ML, Martin P, Borgese F, and Soriani,O

A mutation in the Gardos channel is associated with hereditary xerocytosis. - 2015 - Blood - Rapetti-Mauss R, Lacoste C, Picard V, Guitton C, Pontou-Lombard E, Loosveld M, Nivaggioni V, Dasilva N, Salgado D, Desvignes JP, Béroud C, Viout P, Bernard M, Soriani O, Vinti H, Lacroze V, Feneant-Thibault M, Thuret I, Guizouarn H, and Badens,C

The sigma-1 receptor: a regulator of cancer cell electrical plasticity? - 2013 - Frontiers in physiology - 4 P175 - Crottès D, Guizouarn H, Martin P, Borgese F, and Soriani,O

The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry. - 2012 - The Journal of biological chemistry - 287 P37021-9 - Balasuriya D, Stewart AP, Crottès D, Borgese F, Soriani O, and Edwardson,JM

Band 3 missense mutations and stomatocytosis: insight into the molecular mechanism responsible for monovalent cation leak. - 2011 - Int J Cell Biol - 2011 P136802 - Barneaud-Rocca D, Pellissier B, Borgese F, and Guizouarn,H

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Soriani Olivier
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   Borgese Franck
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    September 2010 - F. Borgese Team
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