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

Stable Identifier
Homo sapiens
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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

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

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

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

Science 2003
Event Information
Orthologous Events
Cross References
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