Roles for the type III TGF-β receptor in human cancer

Transforming growth factor β (TGF-β) superfamily ligands have important roles in regulating cellular homeostasis, embryonic development, differentiation, proliferation, immune surveillance, angiogenesis, motility, and apoptosis in a cell type and context specific manner. TGF-β superfamily signaling pathways also have diverse roles in human cancer, functioning to either suppress or promote cancer progression. The TGF-β superfamily co-receptor, the type III TGF-β receptor (TβRIII, also known as betaglycan) mediates TGF-β superfamily ligand dependent as well as ligand independent signaling to both Smad and non-Smad signaling pathways. Loss of TβRIII expression during cancer progression and direct effects of TβRIII on regulating cell migration, invasion, proliferation, and angiogenesis support a role for TβRIII as a suppressor of cancer progression and/or as a metastasis suppressor. Defining the physiological function and mechanism of TβRIII action and alterations in TβRIII function during cancer progression should enable more effective targeting of TβRIII and TβRIII mediated functions for the diagnosis and treatment of human cancer.