title: Mechanisms of action of bone morphogenetic proteins in cancer.
abstract: The bone morphogenetic proteins (BMPs) play fundamental roles in embryonic development and control differentiation of a diverse set of cell types. It is therefore of no surprise that the BMPs also contribute to the process of tumourigenesis and regulate cancer progression through various stages. We summarise here key roles of BMP ligands, receptors, their signalling mediators, mainly focusing on proteins of the Smad family, and extracellular antagonists, that contribute to the onset of tumourigenesis and to cancer progression in diverse tissues. Overall, the BMP pathways seem to act as tumour suppressors that maintain physiological tissue homeostasis and which are perturbed in cancer either via genetic mutation or via epigenetic misregulation of key gene components. BMPs also control the self-renewal and fate choices made by stem cells in several tissues. By promoting cell differentiation, including inhibition of the process of epithelial-mesenchymal transition, BMPs contribute to the malignant progression of cancer at advanced stages. It is therefore reasonable that pharmaceutical industries continuously develop biological agents and chemical modulators of BMP signalling with the aim to improve therapeutic regimes against several types of cancer.
authors.affiliation: Gastrointestinal Stem Cell Biology Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Hayley
authors.initials: H
authors.lastname: Davis
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Erna
authors.initials: E
authors.lastname: Raja
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.affiliation: Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine, Ehime, Japan; Ludwig Institute for Cancer Research, Science for Life Laboratory, Box 595, Biomedical Center, Uppsala University, 75124 Uppsala, Sweden.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Box 595, Biomedical Center, Uppsala University, 75124 Uppsala, Sweden; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Biomedical Center, Uppsala University, 75123 Uppsala, Sweden. Electronic address: aris.moustakas@imbim.uu.se.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D009363:Neoplasm Proteins; D051785:Smad Proteins
keywords: BMP; Cancer; EMT; Metastasis; TGF-β