Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development
- Authors
- Holtzhausen, A., Golzio, C., How, T., Lee, Y.H., Schiemann, W.P., Katsanis, N., and Blobe, G.C.
- ID
- ZDB-PUB-140127-11
- Date
- 2014
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28(3): 1248-67 (Journal)
- Registered Authors
- Katsanis, Nicholas
- Keywords
- TGF-β, dorsoventral axis, invasion, tumorigenesis
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins/metabolism*
- Humans
- Phosphorylation
- Signal Transduction*
- Smad2 Protein/metabolism*
- Smad3 Protein/metabolism*
- PubMed
- 24308972 Full text @ FASEB J.
The bone morphogenetic protein (BMP) signaling pathways have important roles in embryonic development and cellular homeostasis, with aberrant BMP signaling resulting in a broad spectrum of human disease. We report that BMPs unexpectedly signal through the canonical transforming growth factor β (TGF-β)-responsive Smad2 and Smad3. BMP-induced Smad2/3 signaling occurs preferentially in embryonic cells and transformed cells. BMPs signal to Smad2/3 by stimulating complex formation between the BMP-binding TGF-β superfamily receptors, activin receptor-like kinase (ALK)3/6, and the Smad2/3 phosphorylating receptors ALK5/7. BMP signaling through Smad2 mediates, in part, dorsoventral axis patterning in zebrafish embryos, whereas BMP signaling through Smad3 facilitates cancer cell invasion. Consistent with increased BMP-mediated Smad2/3 signaling during cancer progression, Smad1/5 and Smad 2/3 signaling converge in human cancer specimens. Thus, the signaling mechanisms used by BMPs and TGF-&beta superfamily receptors are broader than previously appreciated.—Holtzhausen, A., Golzio, C., How, T., Lee, Y.-H., Schiemann, W. P., Katsanis, N., Blobe, G. C. Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development.