Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts
With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells

J 2013

Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells

FAFÍLEK, Bohumil; M KRAUSOVA; M VOJTECHOVA; Vendula POSPÍCHALOVÁ; L TUMOVA et al.

Základní údaje

Originální název

Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells

Autoři

Vydání

Gastroenterology, Philadelphia, W B Saunders co-Elsevier Inc, 2013, 0016-5085

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 13.926

Označené pro přenos do RIV

DOI

https://doi.org/10.1053/j.gastro.2012.10.048

UT WoS

000314716300032

Klíčová slova anglicky

Mouse Model of Colon Cancer; beta-Catenin; TCF; Tnfrsf19

Změněno: 31. 3. 2016 12:57, Mgr. Bohumil Fafílek, Ph.D.

Anotace

V originále

BACKGROUND & AIMS: The Wnt signaling pathway is required for maintenance of the intestinal epithelia; blocking this pathway reduces the proliferative capacity of the intestinal stem cells. However, aberrant Wnt signaling leads to intestinal cancer. We investigated the roles of the Wnt pathway in homeostasis of the intestinal epithelium and during malignant transformation in human cells and mice. METHODS: We performed chromatin immunoprecipitation (ChIP) with DNA microarray analysis (ChIP-on-chip) to identify genes regulated by Wnt signaling in human colorectal cancer cells Colo320, DLD1, LS174T, and SW480. Formation of intestinal tumor was induced in C57BL/6J mice using azoxymethane and dextran sulfate. Intestinal tissues from these mice, as well as Apc(+/Min) and Apc(CKO/CKO)/Lgr5-EGFP-IRES-CreERT2 mice, were analyzed by immunohistochemistry and in situ hybridization. RESULTS: We identified promoter regions of 960 genes that interacted with the Wnt pathway nuclear effector T-cell factor 4 in 4 different human colorectal cancer-derived cell lines; 18 of these promoters were present in all chromatin precipitates. Wnt signaling up-regulated a member of the tumor necrosis factor receptor superfamily called TROY. Levels of TROY messenger RNA were increased in human cells with deficiencies in the adenomatous polyposis coli (APC) gene and in cells stimulated with the Wnt3a ligand. Expression of Troy was significantly up-regulated in neoplastic tissues from mice during intestinal tumorigenesis. Lineage tracing experiments revealed that Troy is produced specifically by fast-cycling intestinal stem cells. TROY associated with a unique marker of these cells, leucine-rich repeat-containing G-protein coupled receptor (LGR) 5. In organoids established from the intestinal crypts, Troy suppressed signaling mediated by R-spondin, a Wnt agonist. CONCLUSIONS: TROY is up-regulated in human colorectal cancer cell lines and in intestinal tumors in mice. It functions as a negative modulator of the Wnt pathway in LGR5-positive stem cells.

Citovat

FAFÍLEK, Bohumil; M KRAUSOVA; M VOJTECHOVA; Vendula POSPÍCHALOVÁ; L TUMOVA; E SLONCOVA; M HURANOVA; J STANCIKOVA; A HLAVATA; J SVEC; R SEDLACEK; O LUKSAN; M OLIVERIUS; Ivan VOSKA; Milan JIRSA; J PACES; M KOLAR; M KRIVJANSKA; K KLIMESOVA; H TLASKALOVA-HOGENOVA a V KORINEK. Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells. Gastroenterology. Philadelphia: W B Saunders co-Elsevier Inc, 2013, roč. 144, č. 2, s. 381-391. ISSN 0016-5085. Dostupné z: https://doi.org/10.1053/j.gastro.2012.10.048.

@article{1316069,
   author = {Fafílek, Bohumil and Krausova, M and Vojtechova, M and Pospíchalová, Vendula and Tumova, L and Sloncova, E and Huranova, M and Stancikova, J and Hlavata, A and Svec, J and Sedlacek, R and Luksan, O and Oliverius, M and Voska, Ivan and Jirsa, Milan and Paces, J and Kolar, M and Krivjanska, M and Klimesova, K and TlaskalovaandHogenova, H and Korinek, V},
   article_location = {Philadelphia},
   article_number = {2},
   doi = {https://doi.org/10.1053/j.gastro.2012.10.048},
   keywords = {Mouse Model of Colon Cancer; beta-Catenin; TCF; Tnfrsf19},
   language = {eng},
   issn = {0016-5085},
   journal = {Gastroenterology},
   title = {Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells},
   volume = {144},
   year = {2013}
}

TY  - JOUR
ID  - 1316069
AU  - Fafílek, Bohumil - Krausova, M - Vojtechova, M - Pospíchalová, Vendula - Tumova, L - Sloncova, E - Huranova, M - Stancikova, J - Hlavata, A - Svec, J - Sedlacek, R - Luksan, O - Oliverius, M - Voska, Ivan - Jirsa, Milan - Paces, J - Kolar, M - Krivjanska, M - Klimesova, K - Tlaskalova-Hogenova, H - Korinek, V
PY  - 2013
TI  - Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells
JF  - Gastroenterology
VL  - 144
IS  - 2
SP  - 381-391
EP  - 381-391
PB  - W B Saunders co-Elsevier Inc
SN  - 00165085
KW  - Mouse Model of Colon Cancer
KW  - beta-Catenin
KW  - TCF
KW  - Tnfrsf19
N2  - BACKGROUND & AIMS: The Wnt signaling pathway is required for maintenance of the intestinal epithelia; blocking this pathway reduces the proliferative capacity of the intestinal stem cells. However, aberrant Wnt signaling leads to intestinal cancer. We investigated the roles of the Wnt pathway in homeostasis of the intestinal epithelium and during malignant transformation in human cells and mice. METHODS: We performed chromatin immunoprecipitation (ChIP) with DNA microarray analysis (ChIP-on-chip) to identify genes regulated by Wnt signaling in human colorectal cancer cells Colo320, DLD1, LS174T, and SW480. Formation of intestinal tumor was induced in C57BL/6J mice using azoxymethane and dextran sulfate. Intestinal tissues from these mice, as well as Apc(+/Min) and Apc(CKO/CKO)/Lgr5-EGFP-IRES-CreERT2 mice, were analyzed by immunohistochemistry and in situ hybridization. RESULTS: We identified promoter regions of 960 genes that interacted with the Wnt pathway nuclear effector T-cell factor 4 in 4 different human colorectal cancer-derived cell lines; 18 of these promoters were present in all chromatin precipitates. Wnt signaling up-regulated a member of the tumor necrosis factor receptor superfamily called TROY. Levels of TROY messenger RNA were increased in human cells with deficiencies in the adenomatous polyposis coli (APC) gene and in cells stimulated with the Wnt3a ligand. Expression of Troy was significantly up-regulated in neoplastic tissues from mice during intestinal tumorigenesis. Lineage tracing experiments revealed that Troy is produced specifically by fast-cycling intestinal stem cells. TROY associated with a unique marker of these cells, leucine-rich repeat-containing G-protein coupled receptor (LGR) 5. In organoids established from the intestinal crypts, Troy suppressed signaling mediated by R-spondin, a Wnt agonist. CONCLUSIONS: TROY is up-regulated in human colorectal cancer cell lines and in intestinal tumors in mice. It functions as a negative modulator of the Wnt pathway in LGR5-positive stem cells.
ER  -

FAFÍLEK, Bohumil; M KRAUSOVA; M VOJTECHOVA; Vendula POSPÍCHALOVÁ; L TUMOVA; E SLONCOVA; M HURANOVA; J STANCIKOVA; A HLAVATA; J SVEC; R SEDLACEK; O LUKSAN; M OLIVERIUS; Ivan VOSKA; Milan JIRSA; J PACES; M KOLAR; M KRIVJANSKA; K KLIMESOVA; H TLASKALOVA-HOGENOVA a V KORINEK. Troy, a Tumor Necrosis Factor Receptor Family Member, Interacts With Lgr5 to Inhibit Wnt Signaling in Intestinal Stem Cells. \textit{Gastroenterology}. Philadelphia: W B Saunders co-Elsevier Inc, 2013, roč.~144, č.~2, s.~381-391. ISSN~0016-5085. Dostupné z: https://doi.org/10.1053/j.gastro.2012.10.048.

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