title: NKD1 marks intestinal and liver tumors linked to aberrant Wnt signaling.
abstract: 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.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic; Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Praha 2, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Stancikova
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Krausova
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolar
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Bohumil
authors.initials: B
authors.lastname: Fafilek
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic; Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Srobarova 50, 100 34 Prague 10, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Svec
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Radislav
authors.initials: R
authors.lastname: Sedlacek
authors.affiliation: Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague 4, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Neroldova
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Dobes
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Horazna
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Janeckova
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Vojtechova
authors.affiliation: Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague 4, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Oliverius
authors.affiliation: Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague 4, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Jirsa
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083142 20 Prague 4, Czech Republic. Electronic address: korinek@img.cas.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Korinek
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C424446:Nkd1 protein, mouse; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Colorectal cancer; Hepatocellular carcinoma; Intestine; Liver; NKD1; Wnt signaling