MT1-MMP and MMP-7 in invasion and metastasis of human cancers

Takayuki Shiomi, Yasunori Okada

Research output: Contribution to journalReview articlepeer-review

199 Citations (Scopus)


Previous experimental and biochemical studies on matrix metalloproteinases (MMPs) have indicated that MMPs are implicated in cancer invasion and metastases. Studies on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in various human cancer tissues have further demonstrated that activation of proMMP-2 mediated by a combination of TIM P-2 and MT1-MMP (the proMMP-2/TIMP-2/MT1-MMP system) correlates well with the progression of most of these cancers such as the breast carcinomas, thyroid papillary carcinomas, gastric adenocarcinomas, oral squamous cell carcinomas and gliomas, whereas MMP-7 plays an important role in the metastases of endometrial and gastrointestinal carcinomas. Although MMP-7 is a typical secreted MMP, a member of transmembrane 4 superfamily (TM4SF) captures proMMP-7 on the carcinoma cell membranes through interaction with its propeptide, leading to its pericellular activation. Thus, these results strongly suggest that proteolysis at the cell-extracellular matrix interfaces of cancer cells by the proMMP-2/TIMP-2/MT1-MMP and proMMP-7/TM4SF systems plays crucial roles in the progression of human cancers. In this article, we address the current views on the roles of these MMPs acting on the cell membranes in human cancer invasion and metastases.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalCancer and Metastasis Reviews
Issue number2-3
Publication statusPublished - 2003 Jun 1


  • Human cancers
  • Invasion and metastasis
  • Matrix metalloproteinase-7
  • Membrane-type matrix metalloproteinase
  • Pericellular proteolysis
  • proMMP-2 activation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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