New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: Outside-in signaling and relationship to tumor progression

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• 作者：Brigitte Bauvois ; ^{brigitte.bauvois@crc.jussieu.fr}
• 关键词：MMP ; matrix metalloproteinase ; PEX ; hemopexin-like C-terminal domain ; TIMP ; tissue inhibitor of metalloproteinase ; MT ; membrane type ; CBD ; collagen-binding domain ; ECM ; extracellular matrix ; MMPI ; matrix metalloproteinase inhibitor ; CLL ; chronic lymphocyt
• 刊名：Biochimica et Biophysica Acta (BBA)/Reviews on Cancer
• 出版年：2012
• 出版时间：January, 2012
• 年：2012
• 卷：1825
• 期：1
• 页码：29-36
• 全文大小：459 K

文摘

This review focuses on matrix metalloproteinases (MMPs)-2 (gelatinase A) and -9 (gelatinase B), both of which are cancer-associated, secreted, zinc-dependent endopeptidases. Gelatinases cleave many different targets (extracellular matrix, cytokines, growth factors, chemokines and cytokine/growth factor receptors) that in turn regulate key signaling pathways in cell growth, migration, invasion, inflammation and angiogenesis. Interactions with cell surface integral membrane proteins (CD44, ¦ÁV¦Â/¦Á¦Â1/¦Á¦Â2 integrins and Ku protein) can occur through the gelatinases' active site or hemopexin-like C-terminal domain. This review evaluates the recent literature on the non-enzymatic, signal transduction roles of surface-bound gelatinases and their subsequent effects on cell survival, migration and angiogenesis. Gelatinases have long been drug targets. The current status of gelatinase inhibitors as anticancer agents and their failure in the clinic is discussed in light of these new data on the gelatinases' roles as cell surface transducers ?data that may lead to the design and development of novel, gelatinase-targeting inhibitors.