{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:16:40Z","timestamp":1794003400705,"version":"4.8.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["SPF201909009198"],"award-info":[{"award-number":["SPF201909009198"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 Na<jats:sub>V<\/jats:sub>1.5 voltage-gated sodium channel activity. Indeed, ROCK inhibition enhanced the activity of the pro-invasive Na<jats:sub>V<\/jats:sub>1.5 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.<\/jats:p>","DOI":"10.1038\/s41598-020-70378-3","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T06:03:50Z","timestamp":1596780230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Rock inhibition promotes NaV1.5 sodium channel-dependent SW620 colon cancer cell invasiveness"],"prefix":"10.1038","volume":"10","author":[{"given":"Lucile","family":"Poisson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-8310","authenticated-orcid":false,"given":"Osbaldo","family":"Lopez-Charcas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Chadet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeline","family":"Bon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Lemoine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-1382","authenticated-orcid":false,"given":"Lucie","family":"Brisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Ouaissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Besson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9852-5248","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Roger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driffa","family":"Moussata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"70378_CR1","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","volume":"66","author":"M Arnold","year":"2017","unstructured":"Arnold, M. et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut66, 683\u2013691. https:\/\/doi.org\/10.1136\/gutjnl-2015-310912 (2017).","journal-title":"Gut"},{"key":"70378_CR2","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1016\/S0140-6736(13)61649-9","volume":"383","author":"H Brenner","year":"2014","unstructured":"Brenner, H., Kloor, M. & Pox, C. P. Colorectal cancer. Lancet383, 1490\u20131502. https:\/\/doi.org\/10.1016\/S0140-6736(13)61649-9 (2014).","journal-title":"Lancet"},{"key":"70378_CR3","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cell.2006.11.001","volume":"127","author":"GP Gupta","year":"2006","unstructured":"Gupta, G. P. & Massague, J. Cancer metastasis: building a framework. Cell127, 679\u2013695 (2006).","journal-title":"Cell"},{"key":"70378_CR4","first-page":"6130","volume":"50","author":"IJ Fidler","year":"1990","unstructured":"Fidler, I. J. Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res.50, 6130\u20136138 (1990).","journal-title":"Cancer Res."},{"key":"70378_CR5","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1126\/science.1092053","volume":"302","author":"AJ Ridley","year":"2003","unstructured":"Ridley, A. J. et al. Cell migration: integrating signals from front to back. Science302, 1704\u20131709 (2003).","journal-title":"Science"},{"key":"70378_CR6","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1242\/jcs.114.15.2713","volume":"114","author":"AJ Ridley","year":"2001","unstructured":"Ridley, A. J. Rho GTPases and cell migration. J. Cell Sci.114, 2713\u20132722 (2001).","journal-title":"J. Cell Sci."},{"key":"70378_CR7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00005-015-0382-6","volume":"64","author":"L Wei","year":"2016","unstructured":"Wei, L., Surma, M., Shi, S., Lambert-Cheatham, N. & Shi, J. Novel Insights into the Roles of Rho Kinase in Cancer. Archivum Immunologiae et thErapiae Experimentalis64, 259\u2013278. https:\/\/doi.org\/10.1007\/s00005-015-0382-6 (2016).","journal-title":"Archivum Immunologiae et thErapiae Experimentalis"},{"key":"70378_CR8","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/ncb1019","volume":"5","author":"E Sahai","year":"2003","unstructured":"Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho\/ROCK signalling and extracellular proteolysis. Nat Cell Biol5, 711\u2013719. https:\/\/doi.org\/10.1038\/ncb1019 (2003).","journal-title":"Nat Cell Biol"},{"key":"70378_CR9","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1042\/0264-6021:3540149","volume":"354","author":"T Amano","year":"2001","unstructured":"Amano, T., Tanabe, K., Eto, T., Narumiya, S. & Mizuno, K. LIM-kinase 2 induces formation of stress fibres, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase-catalysed phosphorylation at threonine-505. Biochem. J.354, 149\u2013159. https:\/\/doi.org\/10.1042\/0264-6021:3540149 (2001).","journal-title":"Biochem. J."},{"key":"70378_CR10","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/nrm882","volume":"3","author":"A Bretscher","year":"2002","unstructured":"Bretscher, A., Edwards, K. & Fehon, R. G. ERM proteins and merlin: integrators at the cell cortex. Nat. Rev. Mol. Cell. Biol.3, 586\u2013599. https:\/\/doi.org\/10.1038\/nrm882 (2002).","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"70378_CR11","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1126\/science.273.5272.245","volume":"273","author":"K Kimura","year":"1996","unstructured":"Kimura, K. et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science273, 245\u2013248. https:\/\/doi.org\/10.1126\/science.273.5272.245 (1996).","journal-title":"Science"},{"key":"70378_CR12","doi-asserted-by":"publisher","first-page":"12257","DOI":"10.1074\/jbc.272.19.12257","volume":"272","author":"Y Kureishi","year":"1997","unstructured":"Kureishi, Y. et al. Rho-associated kinase directly induces smooth muscle contraction through myosin light chain phosphorylation. J. Biol. Chem.272, 12257\u201312260. https:\/\/doi.org\/10.1074\/jbc.272.19.12257 (1997).","journal-title":"J. Biol. Chem."},{"key":"70378_CR13","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1126\/science.275.5304.1308","volume":"275","author":"M Amano","year":"1997","unstructured":"Amano, M. et al. Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science275, 1308\u20131311. https:\/\/doi.org\/10.1126\/science.275.5304.1308 (1997).","journal-title":"Science"},{"key":"70378_CR14","first-page":"585","volume":"33","author":"J Lane","year":"2008","unstructured":"Lane, J., Martin, T. A., Watkins, G., Mansel, R. E. & Jiang, W. G. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int. J. Oncol.33, 585\u2013593 (2008).","journal-title":"Int. J. Oncol."},{"key":"70378_CR15","first-page":"3267","volume":"35","author":"J Li","year":"2015","unstructured":"Li, J., Bharadwaj, S. S., Guzman, G., Vishnubhotla, R. & Glover, S. C. ROCK I Has More Accurate Prognostic Value than MET in Predicting Patient Survival in Colorectal Cancer. Anticancer Res.35, 3267\u20133273 (2015).","journal-title":"Anticancer Res."},{"key":"70378_CR16","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1002\/hep.22836","volume":"49","author":"CC Wong","year":"2009","unstructured":"Wong, C. C., Wong, C. M., Tung, E. K., Man, K. & Ng, I. O. Rho-kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion. Hepatology49, 1583\u20131594. https:\/\/doi.org\/10.1002\/hep.22836 (2009).","journal-title":"Hepatology"},{"key":"70378_CR17","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1002\/ijc.26167","volume":"130","author":"P Alhopuro","year":"2012","unstructured":"Alhopuro, P. et al. Candidate driver genes in microsatellite-unstable colorectal cancer. Int. J. Cancer.130, 1558\u20131566. https:\/\/doi.org\/10.1002\/ijc.26167 (2012).","journal-title":"Int. J. Cancer."},{"key":"70378_CR18","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1159\/000341395","volume":"80","author":"I Sari","year":"2013","unstructured":"Sari, I. et al. Role of rho-kinase gene polymorphisms and protein expressions in colorectal cancer development. Pathobiol. J. Immunopathol. Mol. Cell. Biol.80, 138\u2013145. https:\/\/doi.org\/10.1159\/000341395 (2013).","journal-title":"Pathobiol. J. Immunopathol. Mol. Cell. Biol."},{"key":"70378_CR19","doi-asserted-by":"publisher","first-page":"8994","DOI":"10.1158\/0008-5472.CAN-04-2052","volume":"64","author":"DR Croft","year":"2004","unstructured":"Croft, D. R. et al. Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis. Cancer Res.64, 8994\u20139001. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-2052 (2004).","journal-title":"Cancer Res."},{"key":"70378_CR20","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/embor.2012.127","volume":"13","author":"N Rath","year":"2012","unstructured":"Rath, N. & Olson, M. F. Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy. EMBO Rep.13, 900\u2013908. https:\/\/doi.org\/10.1038\/embor.2012.127 (2012).","journal-title":"EMBO Rep."},{"key":"70378_CR21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.imlet.2019.12.012","volume":"219","author":"R Shahbazi","year":"2020","unstructured":"Shahbazi, R. et al. Targeting ROCK signaling in health, malignant and non-malignant diseases. Immunol. Lett.219, 15\u201326. https:\/\/doi.org\/10.1016\/j.imlet.2019.12.012 (2020).","journal-title":"Immunol. Lett."},{"key":"70378_CR22","doi-asserted-by":"publisher","first-page":"13723","DOI":"10.1038\/s41598-017-14216-z","volume":"7","author":"FS Guerra","year":"2017","unstructured":"Guerra, F. S., Oliveira, R. G., Fraga, C. A. M., Mermelstein, C. D. S. & Fernandes, P. D. ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and inhibits cell migration of MDA-MB 231 human breast cancer cells. Sci. Rep.7, 13723. https:\/\/doi.org\/10.1038\/s41598-017-14216-z (2017).","journal-title":"Sci. Rep."},{"key":"70378_CR23","doi-asserted-by":"publisher","first-page":"198","DOI":"10.15252\/emmm.201606743","volume":"9","author":"N Rath","year":"2017","unstructured":"Rath, N. et al. ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. EMBO Mol. Med.9, 198\u2013218. https:\/\/doi.org\/10.15252\/emmm.201606743 (2017).","journal-title":"EMBO Mol. Med."},{"key":"70378_CR24","doi-asserted-by":"publisher","first-page":"e48344","DOI":"10.1371\/journal.pone.0048344","volume":"7","author":"M de Toledo","year":"2012","unstructured":"de Toledo, M., Anguille, C., Roger, L., Roux, P. & Gadea, G. Cooperative anti-invasive effect of Cdc42\/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity. PLoS ONE7, e48344. https:\/\/doi.org\/10.1371\/journal.pone.0048344 (2012).","journal-title":"PLoS ONE"},{"key":"70378_CR25","doi-asserted-by":"publisher","first-page":"3428","DOI":"10.1111\/cas.13786","volume":"109","author":"F Chang","year":"2018","unstructured":"Chang, F. et al. ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells. Cancer Sci.109, 3428\u20133437. https:\/\/doi.org\/10.1111\/cas.13786 (2018).","journal-title":"Cancer Sci."},{"key":"70378_CR26","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/1476-4598-10-79","volume":"10","author":"M Nakashima","year":"2011","unstructured":"Nakashima, M. et al. Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells. Mol. Cancer10, 79. https:\/\/doi.org\/10.1186\/1476-4598-10-79 (2011).","journal-title":"Mol. Cancer"},{"key":"70378_CR27","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ejphar.2010.10.014","volume":"650","author":"S Adachi","year":"2011","unstructured":"Adachi, S. et al. Rho-kinase inhibitor upregulates migration by altering focal adhesion formation via the Akt pathway in colon cancer cells. Eur. J. Pharmacol.650, 145\u2013150. https:\/\/doi.org\/10.1016\/j.ejphar.2010.10.014 (2011).","journal-title":"Eur. J. Pharmacol."},{"key":"70378_CR28","doi-asserted-by":"publisher","first-page":"585","DOI":"10.3892\/ijo_00000533","volume":"36","author":"M Nakashima","year":"2010","unstructured":"Nakashima, M. et al. Rho-kinase regulates negatively the epidermal growth factor-stimulated colon cancer cell proliferation. Int. J. Oncol.36, 585\u2013592. https:\/\/doi.org\/10.3892\/ijo_00000533 (2010).","journal-title":"Int. J. Oncol."},{"key":"70378_CR29","doi-asserted-by":"publisher","first-page":"259142","DOI":"10.1155\/2012\/259142","volume":"2012","author":"R Vishnubhotla","year":"2012","unstructured":"Vishnubhotla, R., Bharadwaj, S., Sun, S., Metlushko, V. & Glover, S. C. Treatment with Y-27632, a ROCK Inhibitor, Increases the Proinvasive Nature of SW620 Cells on 3D Collagen Type 1 Matrix. Int. J. Cell Biol.2012, 259142. https:\/\/doi.org\/10.1155\/2012\/259142 (2012).","journal-title":"Int. J. Cell Biol."},{"key":"70378_CR30","doi-asserted-by":"publisher","first-page":"6957","DOI":"10.1158\/0008-5472.CAN-10-1169","volume":"70","author":"CD House","year":"2010","unstructured":"House, C. D. et al. Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res.70, 6957\u20136967 (2010).","journal-title":"Cancer Res."},{"key":"70378_CR31","doi-asserted-by":"publisher","first-page":"11541","DOI":"10.1038\/srep11541","volume":"5","author":"CD House","year":"2015","unstructured":"House, C. D. et al. Voltage-gated Na+ channel activity increases colon cancer transcriptional activity and invasion via persistent MAPK signaling. Sci. Rep.5, 11541. https:\/\/doi.org\/10.1038\/srep11541 (2015).","journal-title":"Sci. Rep."},{"issue":"Suppl 1","key":"70378_CR32","doi-asserted-by":"publisher","first-page":"i39","DOI":"10.1093\/bja\/aeu104","volume":"113","author":"DT Baptista-Hon","year":"2014","unstructured":"Baptista-Hon, D. T. et al. Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function. Br. J. Anaesth.113(Suppl 1), i39\u2013i48. https:\/\/doi.org\/10.1093\/bja\/aeu104 (2014).","journal-title":"Br. J. Anaesth."},{"key":"70378_CR33","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.yexcr.2017.09.020","volume":"360","author":"M Cascione","year":"2017","unstructured":"Cascione, M. et al. Morphomechanical and structural changes induced by ROCK inhibitor in breast cancer cells. Exp. Cell. Res.360, 303\u2013309. https:\/\/doi.org\/10.1016\/j.yexcr.2017.09.020 (2017).","journal-title":"Exp. Cell. Res."},{"key":"70378_CR34","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1158\/0008-5472.CAN-17-1339","volume":"78","author":"N Rath","year":"2018","unstructured":"Rath, N. et al. Rho Kinase Inhibition by AT13148 Blocks Pancreatic Ductal Adenocarcinoma Invasion and Tumor Growth. Cancer Res.78, 3321\u20133336. https:\/\/doi.org\/10.1158\/0008-5472.CAN-17-1339 (2018).","journal-title":"Cancer Res."},{"key":"70378_CR35","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.tcb.2011.09.006","volume":"21","author":"K Wolf","year":"2011","unstructured":"Wolf, K. & Friedl, P. Extracellular matrix determinants of proteolytic and non-proteolytic cell migration. Trends Cell Biol.21, 736\u2013744. https:\/\/doi.org\/10.1016\/j.tcb.2011.09.006 (2011).","journal-title":"Trends Cell Biol."},{"key":"70378_CR36","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.1242\/jcs.123901","volume":"126","author":"L Brisson","year":"2013","unstructured":"Brisson, L. et al. NaV1.5 Na+ channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia. J. Cell Sci.126, 4835\u20134842 (2013).","journal-title":"J. Cell Sci."},{"key":"70378_CR37","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fphar.2015.00152","volume":"6","author":"S Roger","year":"2015","unstructured":"Roger, S., Gillet, L., Le Guennec, J. Y. & Besson, P. Voltage-gated sodium channels and cancer: is excitability their primary role?. Front Pharmacol.6, 152. https:\/\/doi.org\/10.3389\/fphar.2015.00152 (2015).","journal-title":"Front Pharmacol."},{"key":"70378_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11111675","author":"MBA Djamgoz","year":"2019","unstructured":"Djamgoz, M. B. A., Fraser, S. P. & Brackenbury, W. J. In vivo evidence for voltage-gated sodium channel expression in carcinomas and potentiation of metastasis. Cancers\nhttps:\/\/doi.org\/10.3390\/cancers11111675 (2019).","journal-title":"Cancers"},{"key":"70378_CR39","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1038\/onc.2010.574","volume":"30","author":"L Brisson","year":"2011","unstructured":"Brisson, L. et al. Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene30, 2070\u20132076 (2011).","journal-title":"Oncogene"},{"key":"70378_CR40","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/1476-4598-13-264","volume":"13","author":"V Driffort","year":"2014","unstructured":"Driffort, V. et al. Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization. Mol. Cancer13, 264. https:\/\/doi.org\/10.1186\/1476-4598-13-264 (2014).","journal-title":"Mol. Cancer"},{"key":"70378_CR41","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12943-014-0277-x","volume":"14","author":"M Nelson","year":"2015","unstructured":"Nelson, M., Yang, M., Dowle, A. A., Thomas, J. R. & Brackenbury, W. J. The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Mol. Cancer14, 13. https:\/\/doi.org\/10.1186\/s12943-014-0277-x (2015).","journal-title":"Mol. Cancer"},{"key":"70378_CR42","doi-asserted-by":"publisher","first-page":"32914","DOI":"10.18632\/oncotarget.5441","volume":"6","author":"M Nelson","year":"2015","unstructured":"Nelson, M., Yang, M., Millican-Slater, R. & Brackenbury, W. J. Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo. Oncotarget6, 32914\u201332929. https:\/\/doi.org\/10.18632\/oncotarget.5441 (2015).","journal-title":"Oncotarget"},{"key":"70378_CR43","doi-asserted-by":"publisher","first-page":"18652","DOI":"10.1038\/s41598-019-55197-5","volume":"9","author":"F Gradek","year":"2019","unstructured":"Gradek, F. et al. Sodium channel Nav1.5 controls epithelial-to-mesenchymal transition and invasiveness in breast cancer cells through its regulation by the salt-inducible kinase-1. Sci. Rep.9, 18652. https:\/\/doi.org\/10.1038\/s41598-019-55197-5 (2019).","journal-title":"Sci. Rep."},{"key":"70378_CR44","doi-asserted-by":"publisher","first-page":"8680","DOI":"10.1074\/jbc.M806891200","volume":"284","author":"L Gillet","year":"2009","unstructured":"Gillet, L. et al. Voltage-gated Sodium Channel Activity Promotes Cysteine Cathepsin-dependent Invasiveness and Colony Growth of Human Cancer Cells. J. Biol. Chem.284, 8680\u20138691 (2009).","journal-title":"J. Biol. Chem."},{"key":"70378_CR45","doi-asserted-by":"publisher","first-page":"325","DOI":"10.4161\/chan.21910","volume":"6","author":"WJ Brackenbury","year":"2012","unstructured":"Brackenbury, W. J. Voltage-gated sodium channels and metastatic disease. Channels (Austin)6, 325\u2013361 (2012).","journal-title":"Channels (Austin)"},{"key":"70378_CR46","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.biocel.2006.12.007","volume":"39","author":"S Roger","year":"2007","unstructured":"Roger, S. et al. Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines. Int. J. Biochem. Cell Biol.39, 774\u2013786 (2007).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"70378_CR47","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1002\/ijc.26210","volume":"130","author":"E Hernandez-Plata","year":"2012","unstructured":"Hernandez-Plata, E. et al. Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer. Int. J. Cancer130, 2013\u20132023 (2012).","journal-title":"Int. J. Cancer"},{"key":"70378_CR48","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1002\/jcp.20871","volume":"210","author":"D Diaz","year":"2007","unstructured":"Diaz, D. et al. Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer. J. Cell. Physiol.210, 469\u2013478 (2007).","journal-title":"J. Cell. Physiol."},{"key":"70378_CR49","first-page":"1213","volume":"150","author":"ME Laniado","year":"1997","unstructured":"Laniado, M. E. et al. Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro. Am. J. Pathol.150, 1213\u20131221 (1997).","journal-title":"Am. J. Pathol."},{"key":"70378_CR50","doi-asserted-by":"publisher","first-page":"12995","DOI":"10.1038\/s41598-018-31364-y","volume":"8","author":"O Lopez-Charcas","year":"2018","unstructured":"Lopez-Charcas, O. et al. The invasiveness of human cervical cancer associated to the function of NaV1.6 channels is mediated by MMP-2 activity. Sci. Rep.8, 12995. https:\/\/doi.org\/10.1038\/s41598-018-31364-y (2018).","journal-title":"Sci. Rep."},{"key":"70378_CR51","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.2174\/138161206778522047","volume":"12","author":"S Roger","year":"2006","unstructured":"Roger, S., Potier, M., Vandier, C., Besson, P. & Le Guennec, J. Y. Voltage-gated sodium channels: new targets in cancer therapy?. Curr. Pharm. Des.12, 3681\u20133695 (2006).","journal-title":"Curr. Pharm. Des."},{"key":"70378_CR52","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1016\/j.bbamem.2015.04.013","volume":"2493\u20132501","author":"P Besson","year":"1848","unstructured":"Besson, P. et al. How do voltage-gated sodium channels enhance migration and invasiveness in cancer cells?. Biochim. Biophys. Acta2493\u20132501, 2015. https:\/\/doi.org\/10.1016\/j.bbamem.2015.04.013 (1848).","journal-title":"Biochim. Biophys. Acta"},{"key":"70378_CR53","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10549-012-2102-9","volume":"134","author":"M Yang","year":"2012","unstructured":"Yang, M. et al. Therapeutic potential for phenytoin: targeting Na(v)1.5 sodium channels to reduce migration and invasion in metastatic breast cancer. Breast Cancer Res. Treat.134, 603\u2013615 (2012).","journal-title":"Breast Cancer Res. Treat."},{"key":"70378_CR54","doi-asserted-by":"publisher","first-page":"5381","DOI":"10.1158\/1078-0432.CCR-05-0327","volume":"11","author":"SP Fraser","year":"2005","unstructured":"Fraser, S. P. et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin. Cancer Res.11, 5381\u20135389 (2005).","journal-title":"Clin. Cancer Res."},{"key":"70378_CR55","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.bbamem.2003.07.001","volume":"1616","author":"S Roger","year":"2003","unstructured":"Roger, S., Besson, P. & Le Guennec, J. Y. Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochim. Biophys. Acta1616, 107\u2013111 (2003).","journal-title":"Biochim. Biophys. Acta"},{"key":"70378_CR56","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1016\/j.bmc.2018.04.003","volume":"26","author":"S Dutta","year":"2018","unstructured":"Dutta, S. et al. Discovery and evaluation of nNav1.5 sodium channel blockers with potent cell invasion inhibitory activity in breast cancer cells. Bioorgan. Med. Chem.26, 2428\u20132436. https:\/\/doi.org\/10.1016\/j.bmc.2018.04.003 (2018).","journal-title":"Bioorgan. Med. Chem."},{"key":"70378_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41391-019-0128-3","author":"I Bugan","year":"2019","unstructured":"Bugan, I. et al. Anti-metastatic effect of ranolazine in an in vivo rat model of prostate cancer, and expression of voltage-gated sodium channel protein in human prostate. Prostate Cancer Prostatic Dis.\nhttps:\/\/doi.org\/10.1038\/s41391-019-0128-3 (2019).","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"70378_CR58","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/sj.bjp.0705649","volume":"141","author":"S Roger","year":"2004","unstructured":"Roger, S., Guennec, J. Y. & Besson, P. Particular sensitivity to calcium channel blockers of the fast inward voltage-dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line. Br. J. Pharmacol.141, 610\u2013615 (2004).","journal-title":"Br. J. Pharmacol."},{"key":"70378_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2017.09.002","volume":"183","author":"S Jansen","year":"2018","unstructured":"Jansen, S., Gosens, R., Wieland, T. & Schmidt, M. Paving the Rho in cancer metastasis: Rho GTPases and beyond. Pharmacol. Ther.183, 1\u201321. https:\/\/doi.org\/10.1016\/j.pharmthera.2017.09.002 (2018).","journal-title":"Pharmacol. Ther."},{"key":"70378_CR60","doi-asserted-by":"publisher","first-page":"539","DOI":"10.3892\/ijo.2013.2214","volume":"44","author":"C Dulong","year":"2014","unstructured":"Dulong, C. et al. The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells. Int. J. Oncol.44, 539\u2013547. https:\/\/doi.org\/10.3892\/ijo.2013.2214 (2014).","journal-title":"Int. J. Oncol."},{"key":"70378_CR61","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/labinvest.3700674","volume":"87","author":"R Vishnubhotla","year":"2007","unstructured":"Vishnubhotla, R. et al. ROCK-II mediates colon cancer invasion via regulation of MMP-2 and MMP-13 at the site of invadopodia as revealed by multiphoton imaging. Lab. Invest.87, 1149\u20131158. https:\/\/doi.org\/10.1038\/labinvest.3700674 (2007).","journal-title":"Lab. Invest."},{"key":"70378_CR62","doi-asserted-by":"publisher","first-page":"e99299","DOI":"10.15252\/embj.201899299","volume":"38","author":"F Libanje","year":"2019","unstructured":"Libanje, F. et al. ROCK2 inhibition triggers the collective invasion of colorectal adenocarcinomas. EMBO J.38, e99299. https:\/\/doi.org\/10.15252\/embj.201899299 (2019).","journal-title":"EMBO J."},{"key":"70378_CR63","doi-asserted-by":"publisher","first-page":"17504","DOI":"10.1073\/pnas.0804054105","volume":"105","author":"T Kita","year":"2008","unstructured":"Kita, T. et al. Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target. Proc. Natl. Acad. Sci. USA105, 17504\u201317509. https:\/\/doi.org\/10.1073\/pnas.0804054105 (2008).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"70378_CR64","doi-asserted-by":"publisher","first-page":"13648","DOI":"10.1038\/ncomms13648","volume":"7","author":"E Bon","year":"2016","unstructured":"Bon, E. et al. SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer. Nat. Commun.7, 13648. https:\/\/doi.org\/10.1038\/ncomms13648 (2016).","journal-title":"Nat. Commun."},{"key":"70378_CR65","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods25, 402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262 (2001).","journal-title":"Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70378-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70378-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70378-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T10:27:01Z","timestamp":1670322421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-70378-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["70378"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-70378-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]},"assertion":[{"value":"1 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13350"}}