title: The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells.
abstract: Voltage-gated Na+ channels (VGSCs) are highly expressed in several types of carcinomas including breast, prostate and lung cancers as well as in mesothelioma and cervical cancers. Although the VGSCs activity is considered crucial for the potentiation of cancer cell migration and invasion, the mechanisms responsible for their functional expression and regulation in cancer cells remain unclear. In the present study, the role of the small GTPase RhoA in the regulation of expression and function of the Nav1.5 channel in the breast cancer cell lines MDA-MB 231 and MCF-7 was investigated. RhoA silencing significantly reduced both Nav1.5 channel expression and sodium current indicating that RhoA exerts a stimulatory effect on the synthesis of an active form of Nav1.5 channel in cancer cells. The inhibition of Nav1.5 expression dramatically reduced both cell invasion and proliferation. In addition, a decrease of RhoA protein levels induced by Nav1.5 silencing was observed. Altogether, these findings revealed: i) the key role of the small GTPase RhoA in upregulation of Nav1.5 channel expression and tumor aggressiveness, and ii) the existence of a positive feedback of Nav1.5 channels on RhoA protein levels.
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: C
authors: C
authors: Dulong
authors: Center for Brain Science Research, School of Life Science, Fudan University, P.R. China.
authors: Y J
authors: YJ
authors: Fang
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: C
authors: C
authors: Gest
authors: Center for Brain Science Research, School of Life Science, Fudan University, P.R. China.
authors: M H
authors: MH
authors: Zhou
authors: Unité de Physiopathologie et Médecine Translationnelle, Faculté de Médecine, Strasbourg, France.
authors: C
authors: C
authors: Patte-Mensah
authors: Unité de Physiopathologie et Médecine Translationnelle, Faculté de Médecine, Strasbourg, France.
authors: A G
authors: AG
authors: Mensah-Nyagan
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: J P
authors: JP
authors: Vannier
authors: INSERM UMR-S 728, l'Institut Hématologie, Université Paris 7 Diderot, France.
authors: H
authors: H
authors: Lu
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: C
authors: C
authors: Soria
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: L
authors: L
authors: Cazin
authors: Center for Brain Science Research, School of Life Science, Fudan University, P.R. China.
authors: Y A
authors: YA
authors: Mei
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: R
authors: R
authors: Varin
authors: MERCI, EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen, Rouen, France.
authors: H
authors: H
authors: Li
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D004594:Electrophysiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C568320:SCN5A protein, human; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein