NKD1 marks intestinal and liver tumors linked to aberrant Wnt signaling
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25446263
DOI
10.1016/j.cellsig.2014.11.008
PII: S0898-6568(14)00354-4
Knihovny.cz E-zdroje
- Klíčová slova
- Colorectal cancer, Hepatocellular carcinoma, Intestine, Liver, NKD1, Wnt signaling,
- MeSH
- adaptorové proteiny signální transdukční MeSH
- beta-katenin genetika metabolismus MeSH
- genetická transkripce MeSH
- hepatocelulární karcinom metabolismus patologie MeSH
- hepatocyty metabolismus patologie MeSH
- kolorektální nádory metabolismus patologie MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- mutace MeSH
- myši transgenní MeSH
- myši MeSH
- nádory jater metabolismus patologie MeSH
- protein familiární adenomatózní polypózy nedostatek genetika metabolismus MeSH
- proteiny vázající vápník MeSH
- proteiny Wnt metabolismus MeSH
- signální transdukce MeSH
- střevní nádory metabolismus patologie MeSH
- transportní proteiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adaptorové proteiny signální transdukční MeSH
- beta-katenin MeSH
- CTNNB1 protein, human MeSH Prohlížeč
- messenger RNA MeSH
- Nkd1 protein, mouse MeSH Prohlížeč
- protein familiární adenomatózní polypózy MeSH
- proteiny vázající vápník MeSH
- proteiny Wnt MeSH
- transportní proteiny MeSH
The activity of the Wnt pathway undergoes complex regulation to ensure proper functioning of this principal signaling mechanism during development of adult tissues. The regulation may occur at several levels and includes both positive and negative feedback loops. In the present study we employed one of such negative feedback regulators, naked cuticle homolog 1 (Nkd1), to follow the Wnt pathway activity in the intestine and liver and in neoplasia originated in these organs. Using lineage tracing in transgenic mice we localized Nkd1 mRNA to the bottom parts of the small intestinal crypts and hepatocytes surrounding the central vein of the hepatic lobule. Furthermore, in two mouse models of intestinal tumorigenesis, Nkd1 expression levels were elevated in tumors when compared to healthy tissue. We utilized a collection of human intestinal polyps and carcinomas to confirm that NKD1 represents a robust marker of neoplastic growth. In addition, expression analysis of NKD1 in liver cancer showed that high expression levels of the gene distinguish a subclass of hepatocellular carcinomas related to aberrant Wnt signaling. Finally, our results were confirmed by bioinformatic analysis of large publicly available datasets that included gene expression profiling and high-throughput sequencing data of human colon and liver cancer specimens.
Citace poskytuje Crossref.org
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