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• W2093182474 startingPage "287" @default.
• W2093182474 abstract "Summary Metastatic melanoma remains the deadliest of all skin cancers with a survival rate at five years of less than 15%. MT 1‐ MMP is a membrane‐associated matrix metalloproteinase that controls pericellular proteolysis and is an important, invasion‐promoting, pro‐tumorigenic MMP in cancer. We show that deregulation of MT 1‐ MMP expression happens as early as the transition from nevus to primary melanoma and continues to increase during melanoma progression. Furthermore, MT 1‐ MMP expression is associated with poor melanoma patient outcome, underscoring a pivotal role of MT 1‐ MMP in melanoma pathogenesis. We demonstrate that MT 1‐ MMP is directly required for melanoma cells to metastasize, as cells deprived of MT 1‐ MMP fail to form distant metastasis in an orthotopic mouse melanoma model. We show that MT 1‐ MMP affects cell invasion by activating its target MMP 2. Importantly, we demonstrate, for the first time, that activation of MMP 2 by MT 1‐ MMP is required to sustain RAC 1 activity and promote MT 1‐ MMP ‐dependent cell motility. These data highlight a novel MT 1‐ MMP / MMP 2/ RAC 1 signaling axis in melanoma that may represent an intriguing molecular target for the treatment of invasive melanoma." @default.
• W2093182474 created "2016-06-24" @default.
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• W2093182474 date "2014-01-06" @default.
• W2093182474 modified "2023-09-27" @default.
• W2093182474 title "MT1-MMP modulates melanoma cell dissemination and metastasis through activation of MMP2 and RAC1" @default.
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• W2093182474 doi "https://doi.org/10.1111/pcmr.12201" @default.
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