title: Transforming growth factor β and bone morphogenetic protein actions in brain tumors.
abstract: Members of the transforming growth factor β (TGF-β) family are implicated in the biology of several cancers. Here we focus on malignancies of the brain and examine the TGFβ and the bone morphogenetic protein (BMP) signaling branches of the family. These pathways exhibit context-dependent actions during tumorigenesis, acting either as tumor suppressors or as pro-tumorigenic agents. In the brain, the TGF-βs associate with oncogenic development and progression to the more malignant state. Inversely, the BMPs suppress tumorigenic potential by acting as agents that induce tumor cell differentiation. The latter has been best demonstrated in grade IV astrocytomas, otherwise known as glioblastoma multiforme. We discuss how the actions of TGF-βs and BMPs on cancer stem cells may explain their effects on tumor progression, and try to highlight intricate mechanisms that may link tumor cell differentiation to invasion. The focus on TGF-β and BMP and their actions in brain malignancies provides a rich territory for mechanistic understanding of tumor heterogeneity and suggests ways for improved therapeutic intervention, currently being addressed by clinical trials.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; Ludwig Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden.
authors.forename: Laia
authors.initials: L
authors.lastname: Caja
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; Ludwig Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bellomo
authors.affiliation: Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23 Uppsala, Sweden; Ludwig Cancer Research, Science for Life Laboratory, Uppsala University, Box 595, SE-751 24 Uppsala, Sweden. Electronic address: aris.moustakas@imbim.uu.se.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology*; D005909:Glioblastoma / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D059016:Tumor Microenvironment
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta
keywords: Bone morphogenetic protein; Brain; Cancer; Differentiation; Glioma; Transforming growth factor β