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Modulation de l'échangeur Na + /H + de type 1 (NHE1) par le canal sodique dépendant du voltage Na V 1.5 Implication dans l'invasivité de cellules cancéreuses mammaires humaines

Abstract : Invasive breast cancer cells express NaV1.5 sodium channels which activity seems to be associated with metastatic progression. The activity of the channel in MDA-MB-231 cells leads to a pericellular acidification favourable for the activity of extracellular cysteine cathepsins B and S and for extracellular matrix degradation. During this thesis, we have shown that NHE1 exchanger is the main pH regulator in MDA-MB-231 cells and that the activity of NaV1.5 channels increases protons efflux activity of NHE1 possibly through allosteric modulation. NaV1.5 and NHE1 are co-localised in lipid rafts and in invadopodia of MDA-MB-231 cells. The activity of NHE1 and NaV1.5 promotes the proteolytic activity of invadopodia. Finally, the activity of NaV1.5 channels seems to modulate cytoskeleton and morphology of MDA-MB-231 cancer cells to promote the acquisition of a proinvasive phenotype. In conclusion NaV1.5 increases NHE1 activity in invadopodia to stimulate breast cancer cells invasiveness.
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https://hal-univ-tours.archives-ouvertes.fr/tel-02862877
Contributor : Lucie Brisson <>
Submitted on : Tuesday, June 9, 2020 - 5:36:24 PM
Last modification on : Tuesday, October 20, 2020 - 11:05:58 AM

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Lucie Brisson. Modulation de l'échangeur Na + /H + de type 1 (NHE1) par le canal sodique dépendant du voltage Na V 1.5 Implication dans l'invasivité de cellules cancéreuses mammaires humaines. Biologie cellulaire. Universite François Rabelais de Tours, 2012. Français. ⟨NNT : 2012TOUR4038⟩. ⟨tel-02862877⟩

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