Author Response: Loss of Dnmt3a and Dnmt3b Does Not Affect Epidermal Homeostasis but Promotes Squamous Transformation Through PPAR-γ
March 2017
The study by Rinaldi et al. found that while Dnmt3a and Dnmt3b were not necessary for normal epidermal homeostasis in mice, their loss had significant effects on tumorigenesis. Specifically, the absence of Dnmt3a increased the initiation of squamous tumors, and the combined loss of both Dnmt3a and Dnmt3b led to more aggressive and metastatic squamous carcinomas. Dnmt3a promoted the expression of epidermal differentiation genes and inhibited lipid metabolism genes, including PPAR-γ. Inhibition of PPAR-γ reduced tumorigenesis in the absence of Dnmt3a, indicating that Dnmt3a and Dnmt3b played protective roles against tumorigenesis and that squamous carcinomas were sensitive to PPAR-γ inhibition.
