When MT1-MMP meets ADAMs
DOI: 10.4161/cc.20949
Title: When MT1-MMP meets ADAMs
Journal Title: Cell Cycle
Volume: Volume 11
Issue: Issue 15
Publication Date: August 2012
Start Page: 2793
End Page: 2798
Published online: 27 Oct 2014
ISSN: 1538-4101
Author: Hoi Leong Xavier Wongab, Renhai Caoc, Guoxiang Jinab, Kui Ming Chanab, Yihai Caoc & zhongjun zhou*ab
a Shenzhen Institute of Research and Innovation; The University of Hong Kong; Shenzhen, China
b Department of Biochemistry; Li Ka Shing Faculty of Medicine; The University of Hong Kong; Hong Kong, China
c Department of Microbiology and Tumor Center; Karolinska Institute; Stockholm, Sweden
Abstract: MT1-MMP is a membrane-tethered enzyme capable of remodeling extracellular matrix. MT1-MMP-deficient mice exhibit systematic defects during development, especially in craniofacial development characterized by retarded calvarial bone formation. Recently, we identified MT1-MMP as a critical positive modulator of FGF signaling during intramembranous ossification. MT1-MMP cleaves ADAM9 to protect FGFR2 from ectodomain shedding. Depletion of ADAM9 in MT1-MMP-deficient mice significantly rescued the calvarial defects via restoring FGF signaling. Interestingly, this regulatory mechanism seems to be highly tissue-specific, as defective FGF2-induced corneal angiogenesis in Mmp14?/? mice could not be rescued by removal of ADAM9. In addition, MT1-MMP also cleaves another ADAM family member, ADAM15. Our current findings not only present a novel regulatory mechanism for FGF signaling but also reveal a functional crosstalk between MMP and ADAM families. Better understanding of the interplay between ADAMs and MT1-MMP and its consequences for signaling pathways will provide new insights into therapeutic approaches for the management of developmental disorders and various diseases, such as cancer.
Accepted: 30 May 2012

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