TGFB1 and cancer: Mutation of the downstream TGF-β-BMP ligand-dependent signalling pathway can result in context-dependent and paradoxical gain of function (GOF) of the cancer phenotype, i.e. the ligand activation of the normally functioning signalling pathway exerts a tumour suppressive effect, yet following downstream pathway mutation, ligand activation can then result in ‘oncogenic’ GOF activation, epithelial-mesenchymal transition (EMT) and potent promotion of the invasive and metastatic cancer phenotype1.