TGF-β superfamily co-receptors in cancer

Transforming growth factor-beta (TGF-beta) superfamily signaling via their cognate receptors is frequently modified by TGF-beta superfamily co-receptors. Signaling through SMAD-mediated pathways may be enhanced or depressed depending on the specific co-receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co-receptors from the membrane to generate soluble forms that are often antagonistic to the membrane-bound receptors. The co-receptors discussed here include T beta RIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto-1, MuSK, and RGMs. Dysregulation of these co-receptors can lead to altered TGF-beta superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF-beta superfamily co-receptors on TGF-beta superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co-receptors.

Automated summary

TGF-beta superfamily signaling is often modified by co-receptors, leading to dynamic effects on SMAD-mediated pathways. The release of soluble forms of these co-receptors can further modulate signaling, potentially antagonizing membrane-bound receptors.