國家衛生研究院 NHRI:Item 3990099045/12646
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12646


    Title: DUSP2 regulates extracellular vesicle-VEGF-C secretion and pancreatic cancer early dissemination
    Authors: Wang, CA;Chang, IH;Hou, PC;Tai, YJ;Li, WN;Hsu, PL;Wu, SR;Chiu, WT;Li, CF;Shan, YS;Tsai, SJ
    Contributors: National Institute of Cancer Research
    Abstract: Early dissemination is a unique characteristic and a detrimental process of pancreatic ductal adenocarcinoma (PDAC); however, the underlying mechanism remains largely unknown. Here, we investigate the role of dual-specificity phosphatase-2 (DUSP2)-vascular endothelial growth factor-C (VEGF-C) axis in mediating PDAC lymphangiogenesis and lymphovascular invasion. Expression of DUSP2 is greatly suppressed in PDAC, which results in increased aberrant expression of extracellular vesicle (EV)-associated VEGF-C secretion. EV-VEGF-C exerts paracrine effects on lymphatic endothelial cells and autocrine effects on cancer cells, resulting in the lymphovascular invasion of cancer cells. Tissue-specific knockout of Dusp2 in mouse pancreas recapitulates PDAC phenotype and lymphovascular invasion. Mechanistically, loss-of-DUSP2 enhances proprotein convertase activity and vesicle trafficking to promote the release of the mature form of EV-VEGF-C. Collectively, these findings represent a conceptual advance in understanding pancreatic cancer lymphovascular invasion and suggest that loss-of-DUSP2-mediated VEGF-C processing may play important roles in early dissemination of pancreatic cancer.
    Date: 2020-01
    Relation: Journal of Extracellular Vesicles. 2020 Jan;9(1):Article number 174652.
    Link to: http://dx.doi.org/10.1080/20013078.2020.1746529
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2001-3078&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000523125500001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85082922058
    Appears in Collections:[Others] Periodical Articles

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