TGFB1 and cancer: Briefly, TGF-β ligand binds to TGF-β receptors (type I and II), then Smad2 and Smad3 become phosphorylated, form a complex with Smad4, and this complex translocates into the nucleus, binding to DNA and regulating transcription of its downstream target genes such as repressing the expression of E-cadherin and inducing mesenchymal N-cadherin expression as well as degrading extracellular matrix (ECM), which collectively lead to cancer metastasis [20].