TGF-beta/Smad

TGF-β/SMAD signaling can play a tumor promoting role in advanced cancer and certain essential components of this pathway, TGF-β receptors and SMADs are known to be downregulated via protein ubiquitination by E3 ligases. Multiple DUBs have been shown to target ubiquitinated TGF-β/SMAD signaling components and to be associated with high risk for cancer metastasis, both in animal models and in clinical analysisThe TGF-β superfamily comprises TGF-βs, bone morphogenetic proteins (BMPs), activins and related proteins. These proteins were identified mainly through their roles in development; they regulate the establishment of the body plan and tissue differentiation through their effects on cell proliferation, differentiation and migration.
TGF-β superfamily contains a number of structurally and functionally related secreted cytokines.The TGF-β family members bind to the type I and type II serine/threonine kinase receptors on the cell surface. The serine/threonine kinase receptor family contains twelve members, that are seven type I receptors, also known as activin receptor-like kinases (ALKs), and five type II receptors. In human cancer, TGF-β/SMAD signaling can have a dual role. In the early phase of tumor progression, TGF-β/SMAD plays a tumor suppressing role.TGF-β/SMAD can promote advanced tumor progression such as tumor cell invasion, dissemination/metastasis, and immune evasion. Thus the functional outcome of the TGF-β response is context-dependent and determined both by cell, tissue, and cancer types.