PUBLICATION
Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating β-catenin via a novel C-terminal domain
- Authors
- Chou, Y.T., Jiang, J.K., Yang, M.H., Lu, J.W., Lin, H.K., Wang, H.D., Yuh, C.H.
- ID
- ZDB-PUB-180118-8
- Date
- 2018
- Source
- PLoS Biology 16: e2003714 (Journal)
- Registered Authors
- Yuh, Chiou-Hwa (Cathy)
- Keywords
- none
- MeSH Terms
-
- Adenomatous Polyposis Coli/metabolism
- Adult
- Aged
- Aldose-Ketose Isomerases/metabolism*
- Aldose-Ketose Isomerases/physiology*
- Animals
- Animals, Genetically Modified
- Carcinogenesis
- Cell Line, Tumor
- Cell Nucleus
- Cell Proliferation/physiology
- Cell Transformation, Neoplastic
- Colorectal Neoplasms/genetics
- Colorectal Neoplasms/metabolism
- Female
- Humans
- Male
- Middle Aged
- Phosphorylation
- Promoter Regions, Genetic/genetics
- Protein Domains
- RNA, Messenger/genetics
- Ubiquitination
- Zebrafish
- beta Catenin/genetics
- beta Catenin/physiology*
- PubMed
- 29337987 Full text @ PLoS Biol.
Citation
Chou, Y.T., Jiang, J.K., Yang, M.H., Lu, J.W., Lin, H.K., Wang, H.D., Yuh, C.H. (2018) Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating β-catenin via a novel C-terminal domain. PLoS Biology. 16:e2003714.
Abstract
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 β-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 β-catenin. This association protects β-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 β-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 β-catenin activity and suggests that RPIA might be a biomarker for targeted therapy and prognosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping