GRHL1 and neoplasm: Similarly, in a two-stage chemical skin carcinogenesis model, over 40% of benign papilloma developed into squamous cell carcinoma in Grhl1–/– mice, when compared to one-fourth of such tumor formation in Grhl1+/+ mice, due to the severe impairment of epidermal barrier and aberrant terminal differentiation of keratinocytes (Mlacki et al., 2014).