TGF‐β signaling in development and disease

Abstract

The articles assembled in this especial issue of FEBS Letters review current progress and perspectives on various aspects of transforming growth factor b (TGF-b) signaling in development and disease. A flood of new information emerging at the FASEB Conference on the TGF-b Superfamily, in August 2011, provided impetus for this review series. The new work emphasizes key aspects of the core TGF-b signaling pathway that had long remained obscure. The TGF-b family was identified in the early to mid 1980s, and their basic signal transduction mechanism came to light in the mid 1990s. Building on those pioneer findings, many groups set out to explore the role of this pathway in virtually every major step of embryogenesis from stem cell differentiation to body axis formation and the morphogenesis of tissues and organs. In parallel, an unrelenting effort defined the role of the TGF-b family in the homeostasis of epithelial and endothelial tissues, hematopoietic and immune systems, and skeletal and neural organs. Virtually all cell types were found contain an active TGF-b system regulating cell fate, proliferation, movement, polarity, adhesion, cytokine production, modification of the microenvironment, terminal differentiation and cell death. As the prominence of this pathway became increasingly clear, so did the realization that many aspects of the TGF-b signal transduction process remained inadequately understood. The present set of review articles covers recent progress in recognizing and elucidating these important gaps of knowledge.Wylie In a separate note, Peter Gray and I celebrate the life and key contributions of Wylie Vale, who sadly passed away as the present work was going to press. This issue of FEBS Letters is dedicated in memory of Wylie Vale.

Molecular Mechanisms of Glioma Cell Motility

“…They play a key role in tumor progression and metastasis (149). After binding to the TGF-β receptor (TGFβ-R)-I, TGFβ-RII is phosphorylated.…”

A Search for Genes Mediating the Growth-Promoting Function of TGFβ in the Drosophila melanogaster Wing Disc

“…Essentially, pathway activation results in the generation of a Smad2/Med transcriptional complex that localizes to the nucleus and can interact with the DNA to regulate gene expression. The apparent simplicity from the genetic point of view hides tremendous complexity in the biology of ligand and receptor interactions and in the molecular mechanisms regulating the transcriptional response to the pathway (Feng and Derynck 2005;Massagué 2012). Thus, although the Smad proteins can bind to DNA, the affinity of Smad complexes/DNA is low, and consequently Smad proteins usually associate with other transcriptional regulators to efficiently interact with the regulatory regions of their target genes.…”

Association between the TGFBR2 G-875A Polymorphism and Cancer Risk: Evidence from a Meta-analysis

“…Increased production of TGF-β occurs in various tumor types and is correlated with severity of tumor grade (Massague, 2012a). There is also evidence that TGF-β acts as a suppressor of tumor initiation but as a promoter of tumor progression when the growth inhibition effect of the TGF-β signaling pathway has been overridden by other oncogenic mutations (Massague, 2008;Adorno et al, 2009).…”