Medical Physiology Commons^™

Voltage-Gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity And Invasion Via Persistent Mapk Signaling, Carrie D. House, Bi-Dar Wang, Kristin Ceniccola, Russell Williams, May Simaan, Norman H. Lee, +7 Additional Authors

Pharmacology and Physiology Faculty Publications

Functional expression of voltage-gated Na⁺ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using …