The transcriptional regulators TAZ and YAP direct transforming growth factor β-induced tumorigenic phenotypes in breast cancer cells.

摘要: Uncontrolled transforming growth factor-β (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce tumorigenic events is poorly understood, particularly given that TGFβ has clear tumor suppressing activity other contexts. Here, we demonstrate the transcriptional regulators TAZ and YAP (TAZ/YAP), key effectors of Hippo pathway, necessary promote maintain TGFβ-induced phenotypes cancer cells. Interactions between TAZ/YAP, TGFβ-activated SMAD2/3, TEAD transcription factors reveal convergent roles for these nucleus. Genome-wide expression analyses indicate TEADs, signals coordinate a specific pro-tumorigenic program. Importantly, genes cooperatively regulated by TEAD, TGFβ, such as novel targets NEGR1 UCA1, maintaining Nuclear TAZ/YAP also cooperate with phenotypic changes nontumorigenic cells overcome TGFβ-repressive effects. Our work thus identifies cross-talk nuclear cells, revealing insight into disease-driving mechanisms.