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dc.contributor.authorChou, Yu-Tingen_US
dc.contributor.authorJiang, Jeng-Kaien_US
dc.contributor.authorYang, Muh-Hwaen_US
dc.contributor.authorLu, Jeng-Weien_US
dc.contributor.authorLin, Hua-Kuoen_US
dc.contributor.authorWang, Horng-Daren_US
dc.contributor.authorYuh, Chiou-Hwaen_US
dc.date.accessioned2018-08-21T05:53:15Z-
dc.date.available2018-08-21T05:53:15Z-
dc.date.issued2018-01-01en_US
dc.identifier.issn1545-7885en_US
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pbio.2003714en_US
dc.identifier.urihttp://hdl.handle.net/11536/144452-
dc.description.abstractAltered 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 acids 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 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.en_US
dc.language.isoen_USen_US
dc.titleIdentification 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 domainen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pbio.2003714en_US
dc.identifier.journalPLOS BIOLOGYen_US
dc.citation.volume16en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000423830300011en_US
Appears in Collections:Articles