Differential gene expression by suppression of either SOX2 or TP63 in KYSE70 human esophageal squamous carcinoma cell line.
SOX2 is a transcription factor essential for pluripotent stem cells, and development and maintenance of squamous epithelium. We previously reported SOX2 an oncogene subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs)1.  Here we demonstrate in SCCs that SOX2 interacts with another master squamous transcription factor p63, and through ChIP-seq show that genomic occupancy of SOX2 overlaps with that of p63 at a large number of loci and that they cooperatively regulate gene expression including ETV4, which we find essential for SOX2-amplified SCC cell survival. Furthermore, SOX2 binds to distinct genomic loci in SCCs than in embryonic stem cells and the SOX2-p63 coordinate binding is unique to SCC.  In addition, a subset of SOX2 genomic binding sites in SCC that lack p63 co-occupancy are co-occupied by the AP-1 transcriptional complex.  These demonstrate that SOX2’s actions in SCC differ substantially from its role in pluripotency and identify novel SOX2 interactions that will enable deeper characterization of SOX2’s function in SCC. Overall design: KYSE70 cells with stable expression of either pLKO-Tet-Op-shSOX2 or pLKO-Tet-Op-shTp63 were treated with 50ng/ml of doxycyline for 4 days. Total RNA was extracted, polyA+ selected, reverse transcribed, library constructed and sequencing was performed with Illumina HiSeq 2000. Differencial gene expression between the stable cell lines with Dox-induced and non-Dox treated was analyzed to determine the effects by suppression of either SOX2 or TP63 in KYSE70 cells.