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Rock inhibition promotes NaV1.5 sodium channel-dependent SW620 colon cancer cell invasiveness

Abstract : The acquisition of invasive capacities by carcinoma cells, i.e. their ability to migrate through and to remodel extracellular matrices, is a determinant process leading to their dissemination and to the development of metastases. these cancer cell properties have often been associated with an increased Rho-ROCK signalling, and ROCK inhibitors have been proposed for anticancer therapies. In this study we used the selective ROCK inhibitor, Y-27632, to address the participation of the Rho-ROCK signalling pathway in the invasive properties of SW620 human colon cancer cells. Contrarily to initial assumptions, Y-27632 induced the acquisition of a pro-migratory cell phenotype and increased cancer cell invasiveness in both 3- and 2-dimensions assays. This effect was also obtained using the other ROCK inhibitor Fasudil as well as with knocking down the expression of ROCK-1 or ROCK-2, but was prevented by the inhibition of NaV1.5 voltage-gated sodium channel activity. Indeed, ROCK inhibition enhanced the activity of the pro-invasive NaV1.5 channel through a pathway that was independent of gene expression regulation. In conclusions, our evidence identifies voltage-gated sodium channels as new targets of the ROCK signalling pathway, as well as responsible for possible deleterious effects of the use of ROCK inhibitors in the treatment of cancers.
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Submitted on : Tuesday, September 22, 2020 - 2:10:38 PM
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Lucile Poisson, Osbaldo Lopez-Charcas, Stéphanie Chadet, Emeline Bon, Roxane Lemoine, et al.. Rock inhibition promotes NaV1.5 sodium channel-dependent SW620 colon cancer cell invasiveness. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.13350. ⟨10.1038/s41598-020-70378-3⟩. ⟨inserm-02945554⟩



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