The Ets family of transcription factors regulates a wide range of developmental processes, and many members have been implicated cancer. For example, Ets homologous factor (EHF), an Ets factor expressed solely in epithelia, has been associated with the progression of various cancers, but investigations into its homeostatic function have thus far been limited to in vitro models. Camilla Reehorst, John Mariadason and colleagues now address this shortcoming by generating mouse mutants in which the EHF DNA-binding domain is lost. They find that whole body Ehf mutants are viable but fail to put on weight and develop numerous pathologies after birth. Notably, late-onset epidermal hyperplasia and hyperkeratosis is observed in the skin, while in the colonic epithelium the proliferative colonic crypt compartment is expanded and goblet cell number is reduced. In a model of experimentally induced colitis, the Ehf mutants are much more severely affected than controls, and intestine-specific Ehf knockout causes wide-ranging transcriptional changes, with a specific increase in expression of genes involved in cell cycle progression and epithelial-to-mesenchymal transition. Finally, the authors show that EHF suppresses the growth of Apc-induced colonic adenomas. Thus, EHF promotes homeostasis and suppresses tumour progression in the skin and colonic epithelia.
