Transforming growth factor-ß in tumour development.

ABSTRACT

Transforming growth factor-ß (TGFß) is a ubiquitous cytokine essential for embryonic development and postnatal tissue homeostasis. TGFß signalling regulates several biological processes including cell growth, proliferation, apoptosis, immune function, and tissue repair following injury. Aberrant TGFß signalling has been implicated in tumour progression and metastasis. Tumour cells, in conjunction with their microenvironment, may augment tumourigenesis using TGFß to induce epithelial-mesenchymal transition, angiogenesis, lymphangiogenesis, immune suppression, and autophagy. Therapies that target TGFß synthesis, TGFß-TGFß receptor complexes or TGFß receptor kinase activity have proven successful in tissue culture and in animal models, yet, due to limited understanding of TGFß biology, the outcomes of clinical trials are poor. Here, we review TGFß signalling pathways, the biology of TGFß during tumourigenesis, and how protein quality control pathways contribute to the tumour-promoting outcomes of TGFß signalling.