International journal of oncology, 2014-02, Vol.44 (2), p.539-547
2014
Details
- Autor(en) / Beteiligte
- Titel
- The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells
- Ist Teil von
- International journal of oncology, 2014-02, Vol.44 (2), p.539-547
- Ort / Verlag
- Greece: D.A. Spandidos
- Erscheinungsjahr
- 2014
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1019-6439eISSN: 1791-2423DOI: 10.3892/ijo.2013.2214Titel-ID: cdi_proquest_journals_1932315808
- Format
- –
- Schlagworte
- Apoptosis, Blotting, Western, Breast cancer, Breast Neoplasms - drug therapy, Breast Neoplasms - enzymology, Breast Neoplasms - pathology, Cancer therapies, Cell adhesion & migration, Cell growth, Cell Movement, Cell Proliferation, Drug therapy, Electrophysiology, Female, Gene expression, Gene Expression Regulation, Neoplastic, Genetic aspects, Guanosine triphosphatase, Humans, Immunoenzyme Techniques, invasion, Kinases, Metastasis, Nav1.5 expression, NAV1.5 Voltage-Gated Sodium Channel - chemistry, NAV1.5 Voltage-Gated Sodium Channel - genetics, NAV1.5 Voltage-Gated Sodium Channel - metabolism, Phosphorylation, Physiological aspects, Proteins, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RhoA, rhoA GTP-Binding Protein - antagonists & inhibitors, rhoA GTP-Binding Protein - genetics, rhoA GTP-Binding Protein - metabolism, Risk factors, RNA, Messenger - genetics, RNA, Small Interfering - genetics, Sodium channels, Tumor Cells, Cultured, voltage-gated Na+ channels