When MT1-MMP meets ADAMs

Hoi Leong Xavier Wong, Renhai Cao, Guoxiang Jin, Kui Ming Chan, Yihai Cao, Zhongjun Zhou

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)2793-2798
Number of pages6
JournalCell Cycle
Volume11
Issue number15
DOIs
Publication statusPublished - 2012

User-Defined Keywords

  • Angiogenesis
  • FGF signalling
  • MT1-MMP
  • ADAM9
  • ADAM15
  • osteogenesis

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