Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
1Laboratory of Cancer Genetics and Digestive Diseases, Department of Surgery, Department of Medicine, and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA. 2Department of Veterans Affairs Medical Center, Washington, DC 20007, USA.
The transforming growth factor– (TGF-) superfamily comprises nearly 30 growth and differentiation factors that include TGF-s, activins, inhibins, and bone morphogenetic proteins (BMPs). Multiple members of the TGF- superfamily serve key roles in stem cell fate commitment. The various members of the family can exhibit disparate roles in regulating the biology of embryonic stem (ES) cells and tumor suppression. For example, TGF- inhibits proliferation of multipotent hematopoietic progenitors, promotes lineage commitment of neural precursors, and suppresses epithelial tumors. BMPs block neural differentiation of mouse and human ES cells, contribute to self-renewal of mouse ES cells, and also suppress tumorigenesis. ES cells and tumors may be exposed to multiple TGF- members, and it is likely that the combination of growth factors and cross-talk among the intracellular signaling pathways is what precisely defines stem cell fate commitment. This Connections Map Pathway in the Database of Cell Signaling integrates signaling not only from TGF- and BMP but also from the ligands nodal and activin, and describes the role of the signaling pathways activated by these ligands in mammalian development. Much of the evidence for the connections shown comes from studies on mouse and human ES cells or mouse knockouts. This pathway is important for understanding not only stem cell biology, but also the molecular effectors of TGF- and BMP signaling that may contribute to cancer suppression or progression and thus are potential targets for therapeutic intervention.
The editors suggest the following Related Resources on Science sites:
In Science Signaling
Jason D. Berndt (1 October 2013) Sci. Signal.6 (295), ec235.
[DOI: 10.1126/scisignal.2004767] |Abstract »
Nancy R. Gough (5 February 2008) Sci. Signal.1 (5), ec46.
[DOI: 10.1126/stke.15ec46] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structure of the Bone Morphogenetic Protein Receptor ALK2 and Implications for Fibrodysplasia Ossificans Progressiva.
A. Chaikuad, I. Alfano, G. Kerr, C. E. Sanvitale, J. H. Boergermann, J. T. Triffitt, F. von Delft, S. Knapp, P. Knaus, and A. N. Bullock (2012)
J. Biol. Chem.
|Abstract »|Full Text »|PDF »
Oncogenic KRAS regulates BMP4 expression in colon cancer cell lines.
E.-M. Duerr, Y. Mizukami, K. Moriichi, M. Gala, W.-S. Jo, H. Kikuchi, R. J. Xavier, and D. C. Chung (2012)
Am J Physiol Gastrointest Liver Physiol
|Abstract »|Full Text »|PDF »
Mechanisms and pathways of growth failure in primordial dwarfism.