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dc.contributor.authorChang, C-Yen_US
dc.contributor.authorLin, S-Cen_US
dc.contributor.authorSu, W-Hen_US
dc.contributor.authorHo, C-Men_US
dc.contributor.authorJou, Y-Sen_US
dc.date.accessioned2014-12-08T15:23:15Z-
dc.date.available2014-12-08T15:23:15Z-
dc.date.issued2012-05-01en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/11536/16330-
dc.description.abstractCommon genetic alteration in cancer genomes is implicated for embracing an aberrant cancer gene participated in tumor progression. In this study, we identified a somatic mutated LIM and cysteine-rich domains-1 (LMCD1) as a putative metastatic oncogene in human hepatocellular carcinoma (HCC) using integrated genomic approaches. In addition to revealing genomic amplification and gene upregulation, we identified recurrent E135K (3/48 cases) mutations in HCC tissues and K237R mutation in the PLC/PRF/5 HCC cell line. Expression of mutant LMCD1 E135K or K237R reduced the stress fiber assembly, increased cortical actin accumulation and induced lamellipodial extension. Consistently, these mutations enhanced cell migration and showed activation of the Rac1-signaling pathway. Inhibition of the LMCD1/Rac1 pathway by an LMCD1 short-hairpin RNA (shLMCD1) or the Rac1 inhibitor NSC23766 suppressed the mutation-mediated lamellipodial protrusion and cell migration. In PLC/PRF/5 cells with endogenous K237R mutation, cell migration was enhanced by estrogen-induced LMCD1 expression but reversed by shLMCD1 treatment. Moreover, overexpression of LMCD1 E135K mutation significantly promoted systemic lung metastasis in a murine tail vein injection model. Together, our results suggest that LMCD1 mutations are potential oncogenic events in HCC metastasis to promote cell migration through the Rac1-signaling pathway. Oncogene (2012) 31, 2640-2652; doi:10.1038/onc.2011.440; published online 26 September 2011en_US
dc.language.isoen_USen_US
dc.subjectsomatic mutationsen_US
dc.subjectLMCD1en_US
dc.subjectLIM domainen_US
dc.subjectmetastasisen_US
dc.subjecthepatocellular carcinomaen_US
dc.titleSomatic LMCD1 mutations promoted cell migration and tumor metastasis in hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.identifier.journalONCOGENEen_US
dc.citation.volume31en_US
dc.citation.issue21en_US
dc.citation.epage2640en_US
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.identifier.wosnumberWOS:000304523500004-
dc.citation.woscount5-
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