Smad4-independent TGF-beta signaling in tumor cell migration.
Transforming growth factor-beta (TGF-beta) belongs to a family of multifunctional growth factors that participates in the regulation of a variety of cellular activities. Beside induction of growth inhibition and differentiation of epithelial cells, TGF-beta has been shown to promote epithelial-mesenchymal transition in most epithelial tumors. While inhibition of epithelial cell proliferation in response to TGF-beta is mainly mediated by the well-characterized Smad pathway and subsequent inhibition of gene transcription, the molecular mechanism leading to TGF-beta-induced invasiveness and metastasis of epithelial tumors is less clear. Recent results from several groups suggest that the induction of tumorigenic activity by TGF-beta includes not only signaling by Smads, but also by Rho-GTPases and mitogen-activated protein kinases (MAP kinases). Activation of the MAP kinases extracellular signal-regulated kinases (ERK) 1 and 2 as well as c-jun N-terminal kinase (JNK) has been identified as important steps in TGF-beta-induced, Smad4-independent signal transduction in epithelial cells. Recent results identify a role of activated ERK and JNK and their association with focal complexes in TGF-beta-induced, Smad4-independent cell migration of breast carcinoma cells, and are reviewed here.
Giehl
Klaudia
K
Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany. klaudia.giehl@uni-ulm.de
Imamichi
Yukiko
Y
Menke
Andre
A
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D051901:Smad4 Protein / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases