The epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGF?-SMAD signaling pathway is an inductor of EMT in many tumor types. One hallmark of EMT is downregulation of the adherens junction protein E-cadherin, a process mediated by transcription factors such as the zinc fingers SNAIL and SLUG. Here, we report that the catalytic I?B kinase (IKK) subunit IKK? is necessary for the silencing of E-cadherin in a Panc1 cell model of TGF?-SMAD-mediated EMT, independently of NF?B. IKK? regulates canonical TGF?-SMAD signaling by interacting with SMAD3 and controlling SMAD complex formation on DNA. Furthermore, we demonstrate that the TGF?-IKK?-SMAD signaling pathway induces transcription of the genes encoding SNAIL and SLUG. In addition, we demonstrate that IKK? also modulates canonical TGF?-SMAD signaling in human MDA-MB231 breast cancer cells, arguing for a more general impact of IKK? on the control of TGF?-SMAD signaling. Taken together, these findings indicate that IKK? contributes to the tumor-promoting function of the TGF?-SMAD signaling pathway in particular cancers.     «

The epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGF?-SMAD signaling pathway is an inductor of EMT in many tumor types. One hallmark of EMT is downregulation of the adherens junction protein E-cadherin, a process mediated by transcription factors such as the zinc fingers SNAIL and SLUG. Here, we report that the catalytic I?B kinase (IKK) subunit IKK? is necessary for the silencing of E-cadherin in a Panc1 cell model of TGF?-SMAD-mediated EMT, indepen...     »