國家衛生研究院 NHRI:Item 3990099045/10969
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    题名: Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating beta-catenin via a novel C-terminal domain
    作者: Chou, YT;Jiang, JK;Yang, MH;Lu, JW;Lin, HK;Wang, HD;Yuh, CH
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA modulates cell proliferation and oncogenicity via activation of beta-catenin in colon cancer cell lines. Unlike its role in PPP in which RPIA functions within the cytosol, RPIA enters the nucleus to form a complex with the adenomatous polyposis coli (APC) and beta-catenin. This association protects beta-catenin by preventing its phosphorylation, ubiquitination, and subsequent degradation. The C-terminus of RPIA (amino acid 290 to 311), a region distinct from its enzymatic domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in vitro, RPIA increases the expression of beta-catenin and its target genes, and induces tumorigenesis in gut-specific, promotor-carrying RPIA transgenic (Tg) zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in which RPIA enters the nucleus and stabilizes beta-catenin activity and suggests that RPIA might be a biomarker for targeted therapy and prognosis.
    日期: 2018-01-16
    關聯: PLoS Biology. 2018 Jan 16;16(1):Article number e2003714.
    Link to: http://dx.doi.org/10.1371/journal.pbio.2003714
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1544-9173&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000423830300011
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85041710224
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