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NKD1 mark intestinal and liver tumors

Jitka Stancikova, Michaela Krausova, Michal Kolar, Bohumil Fafilek, Jiri Svec, Radislav Sedlacek, Magdalena Neroldova, Jan Dobes, Monika Horazna, Lucie Janeckova, Martina Vojtechova, Martin Oliverius, Milan Jirsa, Vladimir Korinek

Cellular Signalling


NKD1 is a human gene that encodes the protein Nkd1, a member of the Naked cuticle (Nkd) family of proteins that regulate the Wnt signaling

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 to follow the Wnt pathway activity of the neoplasia originated in these organs.

Using lineage tracing in mice we localized Nkd1 mRNA to the bottom parts of the small intestinal and 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.


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