TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)

Stable Identifier
R-HSA-2173791
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
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In normal cells and in the early stages of cancer development, signaling by TGF-beta plays a tumor suppressive role, as SMAD2/3:SMAD4-mediated transcription inhibits cell division by downregulating MYC oncogene transcription and stimulating transcription of CDKN2B tumor suppressor gene. In advanced cancers however, TGF-beta signaling promotes metastasis by stimulating epithelial to mesenchymal transition (EMT).
TGFBR1 is recruited to tight junctions by binding PARD6A, a component of tight junctions. After TGF-beta stimulation, activated TGFBR2 binds TGFBR1 at tight junctions, and phosphorylates both TGFBR1 and PARD6A. Phosphorylated PARD6A recruits SMURF1 to tight junctions. SMURF1 is able to ubiquitinate RHOA, a component of tight junctions needed for tight junction maintenance, leading to disassembly of tight junctions, an important step in EMT (Wang et al. 2003, Ozdamar et al. 2005).
Literature References
PubMed ID Title Journal Year
15761148 Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity

Ozdamar, B, Bose, R, Barrios-Rodiles, M, Wang, HR, Zhang, Y, Wrana, JL

Science 2005
14657501 Regulation of cell polarity and protrusion formation by targeting RhoA for degradation

Wang, HR, Zhang, Y, Ozdamar, B, Ogunjimi, AA, Alexandrova, E, Thomsen, GH, Wrana, JL

Science 2003
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as an event of
Event Information
Go Biological Process
transforming growth factor beta receptor signaling pathway (0007179)
Orthologous Events
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Bos taurus)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Canis familiaris)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Danio rerio)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Drosophila melanogaster)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Gallus gallus)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Mus musculus)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Rattus norvegicus)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Sus scrofa)
TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (Xenopus tropicalis)
Cross References
BioModels Database
Authored
Orlic-Milacic, M  (2012-04-05)
Reviewed
Huang, T  (2012-05-14)
Chen, YG  (2012-11-14)
Created
Orlic-Milacic, M  (2012-04-02)
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