When BMP Signalling Goes Wrong: The Intracellular and Molecular Mechanisms of BMP Signalling in Cancer

Sivan   Mili   Bokobza; Lin      Ye; Wen   Guo   Jiang

Abstract

Bone Morphogenetic Proteins (BMPs), members of the TGF-β superfamily, are pleiotropic growth factors, known for their role in embryogenesis and bone induction. BMPs signal via two types of serine/threonine kinase BMP receptors (BMPRs), type I, and type II receptors. Ligand binding induces activation of the downstream signalling molecules, the SMADs, which regulate the expression of BMP-responsive genes including those involved in processes such as differentiation, proliferation and apoptosis. BMP signalling is coordinated by both extrinsic and intrinsic mechanisms in order to ensure the control of these important processes. Irregularities however, can occur at any step during the downstream BMP pathway, and aberrations have been implicated in the pathogenesis of several tumour types including: prostate, colorectal, osteosarcomas, myelomas and breast cancer, amongst others. As so many signalling molecules take part in the BMP network, the specific role that these characters play in the pathogenesis of these tumours is rather complex, and hence unclear. In this review, we summarise and consider current literature on BMP signalling, its regulation, and any aberrations in the pathway, focusing on the role of BMPRs, and SMADs on the development, progression and metastasis of solid tumours.

Keywords: Bone morphogenetic protein, signalling, cancer, BMP Receptor, SMAD