Identifying the downstream effectors of E2F7 in squamous cell carcinoma (SCC) cells
Transcriptomics Dataset
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| Accession | GSE58074 |
| Title | Identifying the downstream effectors of E2F7 in squamous cell carcinoma (SCC) cells |
| Description | Advanced head and neck squamous cell carcinomas (HNSCC) are frequently drug resistant and have a mortality rate of 40%%. We have previously shown that E2F7 may contribute to drug sensitivity. In the present study, we conducted an omics screen to identify factors that were responsible for E2F7-dependent resistance to anthracyclines by HNSCC. We provide, in vitro, in vivo and patient data that identifies the existence of a novel E2F7/Sphingosine kinase 1/Sphingosine-1-phosphate/AKT axis that regulates sensitivity to anthracyclines in HNSCC. Specifically, we show that E2F7-dependent sensitivity to doxorubicin occurs via induction of the sphingosine kinase 1/AKT axis. We also show that pharmacological inhibition of Sphingosine kinase 1 or AKT sensitizes SCC cells to the cytotoxic actions of doxorubicin in vitro and in vivo. Combined, these findings highlight a novel mechanism through which SCC cells acquire resistance to anthracyclines and identify specific pharmacological combinations that could be used to treat SCC. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58074 |
| Repository | Gene Expression Omnibus |
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