Moving on: Molecular mechanisms in TGFβ‐induced epithelial cell migration

Abstract

TGFβ, particularly TGFβ1-3, has been shown to promote epithelial dedifferentiation or epithelial-mesenchymal transition (EMT). While inhibition of epithelial cell proliferation in response to TGFβ is mainly mediated by the well-characterised Smad-pathway and subsequent regulation of gene transcription, the molecular mechanisms leading to TGFβ-induced migration, invasion and metastasis of epithelial tumour cells are less clear. Recent results from several groups suggest that the gain of tumourigenic activity by TGFβ includes signalling by mitogen-activated protein kinases (MAP kinases), phosphatidylinositol 3-kinase (PI3-K) and Rho-GTPases. Activation of the MAP kinases extracellular signal-regulated kinase (ERK) 1 and 2, p38 as well as c-jun N-terminal kinase (JNK) has been identified as important steps in TGFβ-induced, Smad4-independent signal transduction in epithelial cells. A role of activated ERK and JNK and their association with focal complexes in TGFβ-induced cell migration and actin cytoskeleton reorganisation of carcinoma cells has been identified recently. In this review we will focus on new data about the molecular mechanisms involved in the TGFβ-induced Smad-independent regulation of epithelial cell migration.