Abstract
Stem cell – like tumor propagating cells self-renew to drive clonal expansion or differentiate into post-mitotic cells without tumorigenic potential in squamous cell carcinomas. This fate choice is governed by a transcriptional network comprised of SOX2-PITX1-TP63 driven self-renewal and KLF4 dependent differentiation circuits. Yet, how stem cell – like tumor propagating cells switch from self-renewal to differentiation remains elusive. Here, we report that this cell fate choice is governed by a bi-stable Klf4 enhancer that is occupied by the transcription factor SOX2 in self-renewing or KLF4 in differentiating squamous cell carcinoma cells, dependent on whether SOX2 is phosphorylated.
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