A Twist-Snail axis critical for TrkB-induced epithelial-mesenchymal transition-like transformation, anoikis resistance, and metastasis.

ABSTRACT: In a genomewide anoikis suppression screen for metastasis genes, we previously identified the neurotrophic receptor tyrosine kinase TrkB. In mouse xenografts, activated TrkB caused highly invasive and metastatic tumors. Here, we describe that TrkB also induces a strong morphological transformation, resembling epithelial-mesenchymal transition (EMT). This required TrkB kinase activity, a functional mitogen-activated protein kinase pathway, suppression of E-cadherin, and induction of Twist, a transcription factor contributing to EMT and metastasis. RNA interference (RNAi)-mediated Twist depletion blocked TrkB-induced EMT-like transformation, anoikis suppression, and growth of tumor xenografts. By searching for essential effectors of TrkB-Twist signaling, we found that Twist induces Snail, an

SUBMITTER: Smit MA 

PROVIDER: S-EPMC2698746 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature