When MT1-MMP meets ADAMs
Volume 11, Issue 15
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August 1, 2012
Pages 2793 - 2798http://dx.doi.org/10.4161/cc.20949
: ADAM15, ADAM9, FGF signaling, MT1-MMP, angiogenesis, osteogenesis
Authors: Hoi Leong Xavier Wong, Renhai Cao, Guoxiang Jin, Kui Ming Chan, Yihai Cao and Zhongjun Zhou View affiliations
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.
Received: May 25, 2012; Accepted: May 30, 2012
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