Monensin Inhibits Canonical Wnt Signaling in Human Colorectal
Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal
Neoplasia Mice

J 2014

Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice

TŮMOVÁ, Lucie; Antonio POMBINHO; Martina VOJTĚCHOVÁ; Jitka STANČÍKOVÁ; Dietmar GRADL et. al.

Základní údaje

Originální název

Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice

Autoři

Vydání

Molecular Cancer Therapeutics, Philadelphia, American Association for Cancer Research, 2014, 1535-7163

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.683

Kód RIV

RIV/00216224:14740/14:00075743

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1158/1535-7163.MCT-13-0625

UT WoS

000334342300005

EID Scopus

2-s2.0-84921273906

Klíčová slova anglicky

BETA-CATENIN; CYCLE ARREST; COLON-CANCER; CARCINOMA-CELLS; LEUKEMIA-CELLS; IN-VIVO; APOPTOSIS; ACTIVATION; APC; GENES

Štítky

kontrola MP, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 9. 2014 11:18, Martina Prášilová

Anotace

V originále

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/beta-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with beta-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or beta-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of beta-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

Citovat

TŮMOVÁ, Lucie; Antonio POMBINHO; Martina VOJTĚCHOVÁ; Jitka STANČÍKOVÁ; Dietmar GRADL; Michaela KRAUSOVÁ; Eva ŠLONCOVÁ; Monika HORÁZNÁ; Vítězslav KŘÍŽ; Olga MACHOŇOVÁ; Jindřich JINDŘICH; Zbyněk ZDRÁHAL; Petr BARTŮNĚK a Vladimír KOŘÍNEK. Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice. Molecular Cancer Therapeutics. Philadelphia: American Association for Cancer Research, 2014, roč. 13, č. 4, s. 812-822. ISSN 1535-7163. Dostupné z: https://doi.org/10.1158/1535-7163.MCT-13-0625.

@article{1186351,
   author = {Tůmová, Lucie and Pombinho, Antonio and Vojtěchová, Martina and Stančíková, Jitka and Gradl, Dietmar and Krausová, Michaela and Šloncová, Eva and Horázná, Monika and Kříž, Vítězslav and Machoňová, Olga and Jindřich, Jindřich and Zdráhal, Zbyněk and Bartůněk, Petr and Kořínek, Vladimír},
   article_location = {Philadelphia},
   article_number = {4},
   doi = {https://doi.org/10.1158/1535-7163.MCT-13-0625},
   keywords = {BETA-CATENIN; CYCLE ARREST; COLON-CANCER; CARCINOMA-CELLS; LEUKEMIA-CELLS; IN-VIVO; APOPTOSIS; ACTIVATION; APC; GENES},
   language = {eng},
   issn = {1535-7163},
   journal = {Molecular Cancer Therapeutics},
   title = {Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice},
   url = {http://mct.aacrjournals.org/content/13/4/812.long},
   volume = {13},
   year = {2014}
}

TY  - JOUR
ID  - 1186351
AU  - Tůmová, Lucie - Pombinho, Antonio - Vojtěchová, Martina - Stančíková, Jitka - Gradl, Dietmar - Krausová, Michaela - Šloncová, Eva - Horázná, Monika - Kříž, Vítězslav - Machoňová, Olga - Jindřich, Jindřich - Zdráhal, Zbyněk - Bartůněk, Petr - Kořínek, Vladimír
PY  - 2014
TI  - Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice
JF  - Molecular Cancer Therapeutics
VL  - 13
IS  - 4
SP  - 812-822
EP  - 812-822
PB  - American Association for Cancer Research
SN  - 15357163
KW  - BETA-CATENIN
KW  - CYCLE ARREST
KW  - COLON-CANCER
KW  - CARCINOMA-CELLS
KW  - LEUKEMIA-CELLS
KW  - IN-VIVO
KW  - APOPTOSIS
KW  - ACTIVATION
KW  - APC
KW  - GENES
UR  - http://mct.aacrjournals.org/content/13/4/812.long
L2  - http://mct.aacrjournals.org/content/13/4/812.long
N2  - The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/beta-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with beta-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or beta-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of beta-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling.
ER  -

TŮMOVÁ, Lucie; Antonio POMBINHO; Martina VOJTĚCHOVÁ; Jitka STANČÍKOVÁ; Dietmar GRADL; Michaela KRAUSOVÁ; Eva ŠLONCOVÁ; Monika HORÁZNÁ; Vítězslav KŘÍŽ; Olga MACHOŇOVÁ; Jindřich JINDŘICH; Zbyněk ZDRÁHAL; Petr BARTŮNĚK a Vladimír KOŘÍNEK. Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice. \textit{Molecular Cancer Therapeutics}. Philadelphia: American Association for Cancer Research, 2014, roč.~13, č.~4, s.~812-822. ISSN~1535-7163. Dostupné z: https://doi.org/10.1158/1535-7163.MCT-13-0625.

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