NKD1 marks intestinal and liver tumors linked to aberrant Wnt signaling
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25446263
DOI
10.1016/j.cellsig.2014.11.008
PII: S0898-6568(14)00354-4
Knihovny.cz E-resources
- Keywords
- Colorectal cancer, Hepatocellular carcinoma, Intestine, Liver, NKD1, Wnt signaling,
- MeSH
- Adaptor Proteins, Signal Transducing MeSH
- beta Catenin genetics metabolism MeSH
- Transcription, Genetic MeSH
- Carcinoma, Hepatocellular metabolism pathology MeSH
- Hepatocytes metabolism pathology MeSH
- Colorectal Neoplasms metabolism pathology MeSH
- Humans MeSH
- RNA, Messenger metabolism MeSH
- Mutation MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Liver Neoplasms metabolism pathology MeSH
- Adenomatous Polyposis Coli Protein deficiency genetics metabolism MeSH
- Calcium-Binding Proteins MeSH
- Wnt Proteins metabolism MeSH
- Signal Transduction MeSH
- Intestinal Neoplasms metabolism pathology MeSH
- Carrier Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- beta Catenin MeSH
- CTNNB1 protein, human MeSH Browser
- RNA, Messenger MeSH
- Nkd1 protein, mouse MeSH Browser
- Adenomatous Polyposis Coli Protein MeSH
- Calcium-Binding Proteins MeSH
- Wnt Proteins MeSH
- Carrier Proteins 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.
References provided by Crossref.org
Wnt Signaling Inhibition Deprives Small Intestinal Stem Cells of Clonogenic Capacity
