TGF-β cytokines regulate cell fate decisions during development, tissue homeostasis and regeneration, and are major players in tumorigenesis, fibrotic disorders, immune malfunctions and various congenital diseases.

Effects of the TGF-β family are mediated by a combinatorial set of ligands and receptors and by a common set of receptor-activated mothers against decapentaplegic homologue (Smad) transcription factors.

Suppression of NK cell-mediated immuno surveillance via the Smad3-E4BP4 axis contributes to tumor development, cancer progression and fibrosis. Disruption of Smad3 is shown to reverse these effects.