HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B
Signaling and Promotes Tissue Damage-Associated Tumorigenesis

J 2015

HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis

JANECKOVA, L; Vendula POSPÍCHALOVÁ; Bohumil FAFÍLEK; M VOJTECHOVA; J TURECKOVA et al.

Základní údaje

Originální název

HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis

Autoři

Vydání

MOLECULAR CANCER RESEARCH, PHILADELPHIA, AMER ASSOC CANCER RESEARCH, 2015, 1541-7786

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.510

Označené pro přenos do RIV

DOI

https://doi.org/10.1158/1541-7786.MCR-15-0033

UT WoS

000358059500008

Změněno: 3. 11. 2015 22:50, RNDr. Vendula Hlaváčková Pospíchalová, Ph.D.

Anotace

V originále

Hypermethylated in cancer 1 (HIC1) represents a prototypic tumor suppressor gene frequently inactivated by DNA methylation in many types of solid tumors. The gene encodes a sequence-specific transcriptional repressor controlling expression of several genes involved in cell cycle or stress control. In this study, a Hic1 allele was conditionally deleted, using a Cre/loxP system, to identify genes influenced by the loss of Hic1. One of the transcripts upregulated upon Hic1 ablation is the toll-like receptor 2 (TLR2). Tlr2 expression levels increased in Hic1-deficient mouse embryonic fibroblasts (MEF) and cultured intestinal organoids or in human cells upon HIC1 knockdown. In addition, HIC1 associated with the TLR2 gene regulatory elements, as detected by chromatin immunoprecipitation, indicating that Tlr2 indeed represents a direct Hic1 target. The Tlr2 receptor senses "danger" signals of microbial or endogenous origin to trigger multiple signaling pathways, including NF-kappa B signaling. Interestingly, Hic1 deficiency promoted NF-kB pathway activity not only in cells stimulated with Tlr2 ligand, but also in cells treated with NF-kappa B activators that stimulate different surface receptors. In the intestine, Hic1 is mainly expressed in differentiated epithelial cells and its ablation leads to increased Tlr2 production. Finally, in a chemical-induced mouse model of carcinogenesis, Hic1 absence resulted in larger Tlr2-positive colonic tumors that showed increased proportion of proliferating cells. (C)2015 AACR.

Citovat

JANECKOVA, L; Vendula POSPÍCHALOVÁ; Bohumil FAFÍLEK; M VOJTECHOVA; J TURECKOVA; J DOBES; M DUBUISSEZ; D LEPRINCE; N BALOGHOVA; M HORAZNA; A HLAVATA; J STANCIKOVA; E SLONCOVA; K GALUSKOVA; H STRNAD a V KORINEK. HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis. MOLECULAR CANCER RESEARCH. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2015, roč. 13, č. 7, s. 1139-1148. ISSN 1541-7786. Dostupné z: https://doi.org/10.1158/1541-7786.MCR-15-0033.

@article{1316068,
   author = {Janeckova, L and Pospíchalová, Vendula and Fafílek, Bohumil and Vojtechova, M and Tureckova, J and Dobes, J and Dubuissez, M and Leprince, D and Baloghova, N and Horazna, M and Hlavata, A and Stancikova, J and Sloncova, E and Galuskova, K and Strnad, H and Korinek, V},
   article_location = {PHILADELPHIA},
   article_number = {7},
   doi = {https://doi.org/10.1158/1541-7786.MCR-15-0033},
   language = {eng},
   issn = {1541-7786},
   journal = {MOLECULAR CANCER RESEARCH},
   title = {HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis},
   url = {http://dx.doi.org/10.1158/1541-7786.MCR-15-0033},
   volume = {13},
   year = {2015}
}

TY  - JOUR
ID  - 1316068
AU  - Janeckova, L - Pospíchalová, Vendula - Fafílek, Bohumil - Vojtechova, M - Tureckova, J - Dobes, J - Dubuissez, M - Leprince, D - Baloghova, N - Horazna, M - Hlavata, A - Stancikova, J - Sloncova, E - Galuskova, K - Strnad, H - Korinek, V
PY  - 2015
TI  - HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis
JF  - MOLECULAR CANCER RESEARCH
VL  - 13
IS  - 7
SP  - 1139-1148
EP  - 1139-1148
PB  - AMER ASSOC CANCER RESEARCH
SN  - 15417786
UR  - http://dx.doi.org/10.1158/1541-7786.MCR-15-0033
L2  - http://dx.doi.org/10.1158/1541-7786.MCR-15-0033
N2  - Hypermethylated in cancer 1 (HIC1) represents a prototypic tumor suppressor gene frequently inactivated by DNA methylation in many types of solid tumors. The gene encodes a sequence-specific transcriptional repressor controlling expression of several genes involved in cell cycle or stress control. In this study, a Hic1 allele was conditionally deleted, using a Cre/loxP system, to identify genes influenced by the loss of Hic1. One of the transcripts upregulated upon Hic1 ablation is the toll-like receptor 2 (TLR2). Tlr2 expression levels increased in Hic1-deficient mouse embryonic fibroblasts (MEF) and cultured intestinal organoids or in human cells upon HIC1 knockdown. In addition, HIC1 associated with the TLR2 gene regulatory elements, as detected by chromatin immunoprecipitation, indicating that Tlr2 indeed represents a direct Hic1 target. The Tlr2 receptor senses "danger" signals of microbial or endogenous origin to trigger multiple signaling pathways, including NF-kappa B signaling. Interestingly, Hic1 deficiency promoted NF-kB pathway activity not only in cells stimulated with Tlr2 ligand, but also in cells treated with NF-kappa B activators that stimulate different surface receptors. In the intestine, Hic1 is mainly expressed in differentiated epithelial cells and its ablation leads to increased Tlr2 production. Finally, in a chemical-induced mouse model of carcinogenesis, Hic1 absence resulted in larger Tlr2-positive colonic tumors that showed increased proportion of proliferating cells. (C)2015 AACR.
ER  -

JANECKOVA, L; Vendula POSPÍCHALOVÁ; Bohumil FAFÍLEK; M VOJTECHOVA; J TURECKOVA; J DOBES; M DUBUISSEZ; D LEPRINCE; N BALOGHOVA; M HORAZNA; A HLAVATA; J STANCIKOVA; E SLONCOVA; K GALUSKOVA; H STRNAD a V KORINEK. HIC1 Tumor Suppressor Loss Potentiates TLR2/NF-kappa B Signaling and Promotes Tissue Damage-Associated Tumorigenesis. \textit{MOLECULAR CANCER RESEARCH}. PHILADELPHIA: AMER ASSOC CANCER RESEARCH, 2015, roč.~13, č.~7, s.~1139-1148. ISSN~1541-7786. Dostupné z: https://doi.org/10.1158/1541-7786.MCR-15-0033.

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