國家衛生研究院 NHRI:Item 3990099045/6902
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 916171      Online Users : 1403
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6902


    Title: Prospero homeobox 1 promotes epithelial-mesenchymal transition in colon cancer cells by inhibiting E-cadherin via miR-9
    Authors: Lu, MH;Huang, CC;Pan, MR;Chen, HH;Hung, WC
    Contributors: National Institute of Cancer Research
    Abstract: PURPOSE: Prospero homeobox 1 (PROX1) has been shown to function as a tumor suppressor in various types of cancer. However, it promotes colon cancer progression. The aim of this study is to clarify the underlying mechanism by which PROX1 regulates tumorigenicity of colon cancer.EXPERIMENTAL DESIGN: Association of PROX1 and clinicopathological features was studied by immunohistochemical staining. Pri-miR-9-2 and miR-9 were detected by quantitative real-time PCR. Assays of cell invasion, adhesion, and matrix metalloproteinase activity were used to study PROX1-mediated epithelial-mesenchymal transition (EMT).RESULTS: PROX1 was overexpressed in 43% (59/136) of colon cancer tissues and its expression was correlated with E-cadherin downregulation (P = 0.00005), advanced tumor staging (P = 0.005), and lymph node metastasis (P = 0.000009). Enforced expression of PROX1 in DLD-1 cells caused downregulation of E-cadherin and integrins and attenuated cell adhesion. These cells showed increase of matrix metalloproteinase activity and invasive ability. Conversely, knockdown of PROX1 in SW620 cells restored E-cadherin protein expression and reduced invasiveness. Unexpectedly, repression of E-cadherin by PROX1 was not mediated by transcriptional inhibition. We found that PROX1 bound to miR-9-2 promoter and triggered its expression to suppress E-cadherin 3'UTR reporter activity and protein expression. Anti-miR-9 restored E-cadherin in SW620 cells, whereas precursor miR-9 inhibited E-cadherin in PROX1-knockdown cells. The miR-9 level was higher in tumor tissues with high PROX1/low E-cadherin than that of tumor tissues with low PROX1/high E-cadherin.CONCLUSIONS: Our results provide mechanistic insights by which PROX1 promotes EMT and colon cancer progression. Targeting of PROX1-mediated oncogenic activity may be helpful for the treatment of colon cancer.
    Date: 2012-11-12
    Relation: Clinical Cancer Research. 2012 Nov 12;18(23):6416-6425.
    Link to: http://dx.doi.org/10.1158/1078-0432.ccr-12-0832
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1078-0432&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000312025600005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84870360174
    Appears in Collections:[Wen-Chun Hung] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    PUB23045246.pdf905KbAdobe PDF257View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback