國家衛生研究院 NHRI:Item 3990099045/9787
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9787


    Title: Vascular endothelial growth factor-C promotes EGFR-TKIs resistance and cancer stemness via SLUG of non-small cell lung cancer
    Authors: Cheng, CC;Su, JL
    Contributors: National Institute of Cancer Research
    Abstract: Background: Acquired resistance to the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, is a critical issue of lung cancer therapy. Vascular endothelial growth factor C (VEGF-C) promote lymphangiognesis and cancer progression but the detailed mechanism related to EGFR-TKIs resistance and cancer stemness remain mostly unclear. Methods: The expression levels of VEGF-C and SLUG in lung cancer patients with gefitinib responder (n = 41) and gefitinib non-responder (n = 39) were examined by quantitative RT-PCR and Oncomine database analysis. The effect of VEGF-C and SLUG on EGFR-TKIs resistance by MTT assay and cancer-stem-like properties by quantitative RT-PCR in vitro.Results: In this study, we observed that high level of VEGF-C correlated to EGFR mutation-independent gefitinib resistance and cancer-stem-like properties in vitro and in vivo; lung cancer patients with high VEGF-C expression had high level of cancer stem cell markers and worst progression-free survival. Moreover, we found a transcription factor, SLUG, involved in VEGF-C/VEGFR3-induced gefitinib resistance and cancer stemness of lung cancer.Conclusions: These results suggest that VEGF-C is a critical role for EGFR-TKIs resistance and cancer stemness of lung cancer, and targeting VEGF-C/VEGFR3/SLUG pathway may provide a potential therapeutic strategy for lung cancer patient with acquired resistance to EGFR-TKIs.
    Date: 2016-04
    Relation: Journal of Thoracic Oncology. 2016 Apr;11(4, Suppl.):S132-133.
    Link to: http://dx.doi.org/10.1016/s1556-0864(16)30283-0
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1556-0864&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000412866300169
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85044287203
    Appears in Collections:[Jen-Liang Su] Conference Papers/Meeting Abstract

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