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- _3 value "Histone deacetylase (HDAC) inhibitors are known toexert antimetastatic and antiangiogenic activity in vitro and in vivo. RECK is a membrane-anchored glycoprotein that negatively regulates matrixmetalloproteinases (MMPs) and inhibits tumor metastasis and angiogenesis. Inthis study, we test the possibility that HDAC inhibitor may increase RECKexpression to inhibit MMP activation and cancer cell invasion. Our resultsshowed that trichostatin A (TSA) up-regulated RECK via transcriptionalactivation in CL-1 human lung cancer cells. Flow cytometric analysisdemonstrated that RECK protein on cell surface was increased after treatment ofTSA. Moreover, up-regulation of RECK expression by TSA attenuated MMP-2activity. To explore whether HDAC inhibitor-induced inhibition of MMP-2activation is indeed mediated via RECK, we used small interference RNA (siRNA)to block RECK expression and found that inhibition of RECK by siRNA abolishedthe inhibitory effect of TSA on MMP-2 activation. In addition, TSA suppressedthe invasive ability of CL-1 cells. Taken together, this study reveals a novelmechanism by which HDAC inhibitors suppress tumor invasion and provides a newstrategy for cancer therapy." provenance.
- _3 wasQuotedFrom 12810630 provenance.