The dynamic roles of TGF-β in cancer.
The transforming growth factor-β (TGF-β) signalling pathway plays a critical and dual role in the progression of human cancer. During the early phase of tumour progression, TGF-β acts as a tumour suppressor, exemplified by deletions or mutations in the core components of the TGF-β signalling pathway. On the contrary, TGF-β also promotes processes that support tumour progression such as tumour cell invasion, dissemination, and immune evasion. Consequently, the functional outcome of the TGF-β response is strongly context-dependent including cell, tissue, and cancer type. In this review, we describe the molecular signalling pathways employed by TGF-β in cancer and how these, when perturbed, may lead to the development of cancer. Concomitantly with our increased appreciation of the molecular mechanisms that govern TGF-β signalling, the potential to therapeutically target specific oncogenic sub-arms of the TGF-β pathway increases. Indeed, clinical trials with systemic TGF-β signalling inhibitors for treatment of cancer patients have been initiated. However, considering the important role of TGF-β in cardiovascular and many other tissues, careful screening of patients is warranted to minimize unwanted on-target side effects.
Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands.
Erik
E
Meulmeester
Peter
P
Ten Dijke
D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D009363:Neoplasm Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta