國家衛生研究院 NHRI:Item 3990099045/9576
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    題名: A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination
    作者: Ahronian, LG;Zhu, LJ;Chen, YW;Chu, HC;Klimstra, DS;Lewis, BC
    貢獻者: National Institute of Cancer Research
    摘要: The presence of invasion into the extra-hepatic portion of the portal vein or the development of distant metastases renders hepatocellular carcinoma (HCC) patients ineligible for the only potential curative options for this malignancy-tumor resection or organ transplantation. Gene expression profiling of murine HCC cell lines identified KLF6 as a potential regulator of HCC cell migration. KLF6 knockdown increases cell migration, consistent with the correlation between decreased KLF6 mRNA levels and the presence of vascular invasion in human HCC. Concordantly, single-copy deletion of Klf6 in a HCC mouse model results in increased tumor formation, increased metastasis to the lungs and decreased survival, indicating that KLF6 suppresses both HCC development and metastasis. By combining gene expression profiling and chromatin immunoprecipitation coupled to deep sequencing, we identified novel transcriptional targets of KLF6 in HCC cells including VAV3, a known activator of the RAC1 small GTPase. Indeed, RAC1 activity is increased in KLF6-knockdown cells in a VAV3-dependent manner, and knockdown of either RAC1 or VAV3 impairs HCC cell migration. Together, our data demonstrate a novel function for KLF6 in constraining HCC dissemination through the regulation of a VAV3-RAC1 signaling axis.
    日期: 2016-09
    關聯: Oncogene. 2016 Sep;35(35):4653-4662.
    Link to: http://dx.doi.org/10.1038/onc.2016.2
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000382336300011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84958087554
    顯示於類別:[陳雅雯] 期刊論文

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