title: Regulation of the TGF-β pathway by deubiquitinases in cancer.
abstract: The transforming growth factor-β (TGF-β) pathway regulates diverse cellular processes. It signals via serine/threonine kinase receptors and intracellular Smad and non-Smad effector proteins. In cancer cells, aberrant TGF-β signalling can lead to loss of growth inhibition and an increase in invasion, epithelial-to-mesenchymal transition (EMT) and metastasis. Therapeutic targeting of the pro-oncogenic TGF-β responses is currently being explored as a potential therapy against certain invasive and metastatic cancer types. The ubiquitin post-translational regulation system is emerging as a key regulatory mechanism for the control of TGF-β pathway components. In this review, we focus on the role of deubiquitinases (DUBs), which counteract the activity of E3 ubiquitin ligases. We will discuss the mechanisms by which specific DUBs control Smad and non-Smad TGF-β signalling routes, and how perturbation of the expression and function of DUBs contributes to misregulation of TGF-β signalling in cancer.
authors.affiliation: Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Sijia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: de Boeck
authors.affiliation: Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: van Dam
authors.affiliation: Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Centre, Leiden, The Netherlands; Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, 75124, Uppsala, Sweden. Electronic address: p.ten_dijke@lumc.nl.
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Dijke
mesh_terms: D000818:Animals; D000072017:Deubiquitinating Enzymes / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D000072017:Deubiquitinating Enzymes
keywords: Cancer; Deubiquitinase; Smad; TGF-β; Ubiquitin