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The TGFβ ligands signal through the type I and type II TGFβ receptors. Canonical signaling proceeds with phosphorylation of Smad2 and Smad3, which then combine with Smad4 to enter the nucleus to mediate growth inhibition. Smad7 is a negative mediator in this process. In addition, TGFβ binding to its receptors activates many noncanonical signaling pathways and regulates tumor cell migration and metastasis.
