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- W2129484112 abstract "Growth factors and cytokines perform an important role in the etiology and progression of a number of different types of cancer (1,2). These peptides can function either as cis/autocrine or as trans/paracrine effectors for tumor cells and/or for different types of surrounding host cells that can influence tumor initiation, progression, and metastasis. The transforming growth factor β (TGF-β) superfamily, which is found in all metazoans, consists of 30 distinct ligands that include TGF-βs, activins, Nodal, bone morphogenetic proteins, and growth and differentiation factors (3). In mammals there are three different, highly homologous TGF-β isoforms, TGF-β1, TGF-β2, and TGF-β3, that are initially synthesized from a large inactive/latent precursor bound to other proteins and that need to be proteolytically processed by proprotein convertases to produce biologically active dimeric ligands. Activation of canonical (Smad-dependent) and noncanonical (Smad-independent) pathways by all members of this superfamily requires ligand binding to one of five distinct members of the type 2 serine/threonine kinase receptors and subsequent heterodimerization and serine/threonine transphosphorylation of one of seven different type 1 serine/threonine kinase receptors (3,4). For some ligands, additional coreceptors (eg, Cripto-1/Cryptic, endoglin, betaglycan, and Dragon) are needed for optimal ligand binding to and activation of the type 2–-type 1 receptor heterodimeric receptor complex. Reciprocally, there are inhibitory proteins (eg, Lefty, CD-109, BAMBI, COCO, Chordin, and Cerberus) that can bind to either ligands and/or the receptors and effectively antagonize signaling through this pathway (5,6)." @default.
- W2129484112 created "2016-06-24" @default.
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- W2129484112 date "2014-02-07" @default.
- W2129484112 modified "2023-09-27" @default.
- W2129484112 title "Transforming Growth Factor in Cancer: Janus, the Two-Faced God" @default.
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- W2129484112 doi "https://doi.org/10.1093/jnci/djt441" @default.
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