Squamous cell carcinomas (SCCs) of the skin and head and neck frequently recur after therapy, a process driven in part by TGF-β-responding CSCs that exhibit invasive, poorly differentiated, and quiescent phenotypes. Although TGF-β-responding CSCs promote SCC progression and recurrence, whether invasive and quiescent states are regulated by changes in chromatin accessibility has remained unclear. A central finding of this dissertation is that TGF-β-responding CSCs acquire a distinct set of newly accessible chromatin regions during progression to invasive SCC, activating a transcriptional program that promotes invasion and quiescence.
