NOTCH1 and neoplasm: Since cellular origins of BCC and cSCC can be the same (see above), GLI1 downregulation may result in the induction of an alternative (tumor) stem cell fate decision, which—if the stem cell has acquired mutations in cSCC-driving oncogenes or tumor suppressor genes such as RAS, TP53, NOTCH1/2, or MLL3 (Pickering et al., 2014)—results in the appearance of a squamous phenotype.