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 (T β RIII, 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 T β RIII expression during cancer progression and direct effects of T β RIII on regulating cell migration, invasion, proliferation, and angiogenesis support a role for T β RIII as a suppressor of cancer progression and/or as a metastasis suppressor. Defining the physiological function and mechanism of T β RIII action and alterations in T β RIII function during cancer progression should enable more effective targeting of T β RIII and T β RIII mediated functions for the diagnosis and treatment of human cancer.