Novel bone morphogenetic protein signaling through Smad2 and Smad3 to regulate cancer progression and development

作者：Holtzhausen Alisha; Golzio Christelle; How Tam; Lee Yong Hun; Schiemann William P; Katsanis Nicholas; Blobe Gerard C^*

来源：The FASEB Journal, 2014, 28(3): 1248-1267.

DOI：10.1096/fj.13-239178

• TGF-
• tumorigenesis
• invasion
• dorsoventral axis

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 (TGF-)-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- 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- 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.

• 出版日期2014-3