While our own published findings and those of others have implicated Notch1 as a tumor promoter in SCCs12, 54–56, the current study is the first to demonstrate in vivo that Notch1 facilitates tumor initiation by converting CD44L cells to highly tumorigenic CD44H cells with mesenchymal traits, complementing the earlier studies implicating EMT and ZEB1 in the CD44L-to-CD44H transition24, 28, 57. Here, ZEB1 is linked to neoplasm.