No transcriptional evidence for active Na_v channels in two classes of cancer cell

Abstract

Voltage-gated sodium channel (Na v ) expression in non-excitable cells has raised questions regarding their non-canonical roles. Interestingly, a growing body of evidence also points towards the prevalence of aberrant Na v expression in malignant tumors, potentially opening a new therapeutic window. In this study, the transcriptional consequences of channel inhibition were investigated in non-small cell lung carcinoma H460 and neuroblastoma SH-SYSY cell lines, that both express Na v 1.7. Channel activity was blocked by the application of both selective, ProTx-II, and non-selective, tetrodotoxin, inhibitors. Global gene expression profiling did not point to any statistically significant inhibition-associated perturbation of the transcriptome. A small subset of genes that showed relatively consistent changes across multiple treatments were further assayed in the context of a multiplex bead expression array which failed to recapitulate the changes seen in the global array. We conclude that there is no robust transcriptional signature associated with the inhibition of two sodium channel expressing cancer cell lines and consequently sodium channel inhibition will not lend itself to therapeutic approaches such as transcription-based drug repurposing.

Transcription Profile And Pathway Analysis Of The Endocannabinoid Receptor Inverse Agonist AM630 In The Core And Infiltrative Boundary Of Human Glioblastoma Cells

“…The resulting profile is the gene rank profile (GRP). This analysis is consistent with that presented by Hompoonsup et al [23].…”

“…Cell functionality is encoded in the expressed genes and relative expression can be quantified by comparing the probe level ranks in the samples relative to their ranks across multiple samples profiled on the same array platform, to generate a GRP [23], see Methods. Comparing the GRP with similar profiles for multiple cancer cell lines from The Cancer Genome Atlas (TCGA) (https://cancergenome.nih.gov/) further strengthens our understanding of the basal transcriptomic profile of the core cell population, see Table 1.…”

Transcription Profile and Pathway Analysis of the Endocannabinoid Receptor Inverse Agonist AM630 in the Core and Infiltrative Boundary of Human Glioblastoma Cells

“…The resulting profile is the gene rank profile (GRP). This analysis is the same as that presented by Hompoonsup et al [ 23 ]. The rank profiles for the U87 and GIN-8 cells are given in Table S1 .…”

“…Expression ultimately only has meaning in relation to levels seen in other cellular contexts. Thus we quantified gene expression by comparing the probe level ranks in the samples relative to their ranks across multiple samples profiled on the same array platform, to generate a GRP [ 23 ]; see Methods. Comparing the GRP with similar profiles for multiple cancer cell lines from The Cancer Genome Atlas (TCGA) ( , accessed on 20 December 2021) further strengthens our understanding of the basal transcriptomic profile of the core cell population (see Table 1 ).…”