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| Home > Publications database > Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance. > print |
| Home > Publications database > Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance. > print |
| 001 | 127785 | ||
| 005 | 20240228140949.0 | ||
| 024 | 7 | _ | |a 10.1038/ncomms9904 |2 doi |
| 024 | 7 | _ | |a pmid:26603103 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC4674781 |2 pmc |
| 024 | 7 | _ | |a altmetric:4811043 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2017-03807 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Wickström, Malin |b 0 |
| 245 | _ | _ | |a Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance. |
| 260 | _ | _ | |a London |c 2015 |b Nature Publishing Group |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1508923338_22424 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is commonly overexpressed in cancers and is implicated in the development of chemoresistance. The use of drugs inhibiting MGMT has been hindered by their haematologic toxicity and inefficiency. As a different strategy to inhibit MGMT we investigated cellular regulators of MGMT expression in multiple cancers. Here we show a significant correlation between Wnt signalling and MGMT expression in cancers with different origin and confirm the findings by bioinformatic analysis and immunofluorescence. We demonstrate Wnt-dependent MGMT gene expression and cellular co-localization between active β-catenin and MGMT. Pharmacological or genetic inhibition of Wnt activity downregulates MGMT expression and restores chemosensitivity of DNA-alkylating drugs in mouse models. These findings have potential therapeutic implications for chemoresistant cancers, especially of brain tumours where the use of temozolomide is frequently used in treatment. |
| 536 | _ | _ | |a 312 - Functional and structural genomics (POF3-312) |0 G:(DE-HGF)POF3-312 |c POF3-312 |f POF III |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a 2-(4-(2-methylpyridin-4-yl)phenyl)-N-(4-(pyridin-3-yl)phenyl)acetamide |2 NLM Chemicals |
| 650 | _ | 7 | |a Antineoplastic Agents |2 NLM Chemicals |
| 650 | _ | 7 | |a Benzeneacetamides |2 NLM Chemicals |
| 650 | _ | 7 | |a G007-LK |2 NLM Chemicals |
| 650 | _ | 7 | |a Heterocyclic Compounds, 3-Ring |2 NLM Chemicals |
| 650 | _ | 7 | |a LGK974 |2 NLM Chemicals |
| 650 | _ | 7 | |a Pyrans |2 NLM Chemicals |
| 650 | _ | 7 | |a Pyrazines |2 NLM Chemicals |
| 650 | _ | 7 | |a Pyridines |2 NLM Chemicals |
| 650 | _ | 7 | |a Sulfones |2 NLM Chemicals |
| 650 | _ | 7 | |a Triazoles |2 NLM Chemicals |
| 650 | _ | 7 | |a Tumor Suppressor Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Wnt Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a XAV939 |2 NLM Chemicals |
| 650 | _ | 7 | |a beta Catenin |2 NLM Chemicals |
| 650 | _ | 7 | |a irinotecan |0 0H43101T0J |2 NLM Chemicals |
| 650 | _ | 7 | |a Vincristine |0 5J49Q6B70F |2 NLM Chemicals |
| 650 | _ | 7 | |a salinomycin |0 62UXS86T64 |2 NLM Chemicals |
| 650 | _ | 7 | |a Dacarbazine |0 7GR28W0FJI |2 NLM Chemicals |
| 650 | _ | 7 | |a Doxorubicin |0 80168379AG |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA Modification Methylases |0 EC 2.1.1.- |2 NLM Chemicals |
| 650 | _ | 7 | |a MGMT protein, human |0 EC 2.1.1.63 |2 NLM Chemicals |
| 650 | _ | 7 | |a Glucose-6-Phosphate Isomerase |0 EC 5.3.1.9 |2 NLM Chemicals |
| 650 | _ | 7 | |a DNA Repair Enzymes |0 EC 6.5.1.- |2 NLM Chemicals |
| 650 | _ | 7 | |a Celecoxib |0 JCX84Q7J1L |2 NLM Chemicals |
| 650 | _ | 7 | |a Cisplatin |0 Q20Q21Q62J |2 NLM Chemicals |
| 650 | _ | 7 | |a Camptothecin |0 XT3Z54Z28A |2 NLM Chemicals |
| 650 | _ | 7 | |a temozolomide |0 YF1K15M17Y |2 NLM Chemicals |
| 700 | 1 | _ | |a Dyberg, Cecilia |b 1 |
| 700 | 1 | _ | |a Milosevic, Jelena |b 2 |
| 700 | 1 | _ | |a Einvik, Christer |b 3 |
| 700 | 1 | _ | |a Calero, Raul |0 0000-0003-1525-1921 |b 4 |
| 700 | 1 | _ | |a Sveinbjörnsson, Baldur |b 5 |
| 700 | 1 | _ | |a Sandén, Emma |b 6 |
| 700 | 1 | _ | |a Darabi, Anna |0 0000-0003-4326-8149 |b 7 |
| 700 | 1 | _ | |a Siesjö, Peter |b 8 |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 9 |u dkfz |
| 700 | 1 | _ | |a Kogner, Per |b 10 |
| 700 | 1 | _ | |a Baryawno, Ninib |b 11 |
| 700 | 1 | _ | |a Johnsen, John Inge |b 12 |
| 773 | _ | _ | |a 10.1038/ncomms9904 |g Vol. 6, p. 8904 - |0 PERI:(DE-600)2553671-0 |p 8904 - |t Nature Communications |v 6 |y 2015 |x 2041-1723 |
| 909 | C | O | |o oai:inrepo02.dkfz.de:127785 |p VDB |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 9 |6 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |
| 913 | 1 | _ | |a DE-HGF |l Krebsforschung |1 G:(DE-HGF)POF3-310 |0 G:(DE-HGF)POF3-312 |2 G:(DE-HGF)POF3-300 |v Functional and structural genomics |x 0 |4 G:(DE-HGF)POF |3 G:(DE-HGF)POF3 |b Gesundheit |
| 914 | 1 | _ | |y 2015 |
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| 915 | _ | _ | |a Creative Commons Attribution CC BY (No Version) |0 LIC:(DE-HGF)CCBYNV |2 V:(DE-HGF) |b DOAJ |
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| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1060 |2 StatID |b Current Contents - Agriculture, Biology and Environmental Sciences |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |
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