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| Home > Publications database > The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma. > print |
| 001 | 120198 | ||
| 005 | 20240228135017.0 | ||
| 024 | 7 | _ | |a 10.1038/nm.3666 |2 doi |
| 024 | 7 | _ | |a pmid:25150496 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC4334261 |2 pmc |
| 024 | 7 | _ | |a 1078-8956 |2 ISSN |
| 024 | 7 | _ | |a 1546-170X |2 ISSN |
| 024 | 7 | _ | |a altmetric:2632651 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2017-00780 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a He, Xuelian |b 0 |
| 245 | _ | _ | |a The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog-driven medulloblastoma. |
| 260 | _ | _ | |a New York, NY |c 2014 |b Nature America Inc. |
| 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 1491476353_16890 |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 Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G protein Gαs, as a potent tumor suppressor gene that, when expressed at low levels, defines a subset of aggressive Sonic hedgehog (SHH)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically distinct progenitors in mice is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. Gαs is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation in levels of a Gαs effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas-ablated mice. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for Gαs that can be found consistently across Shh-group medulloblastomas of disparate cellular and anatomical origins, highlighting G protein modulation as a potential therapeutic avenue. |
| 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 Hedgehog Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Cyclic AMP |0 E0399OZS9N |2 NLM Chemicals |
| 650 | _ | 7 | |a GTP-Binding Protein alpha Subunits, Gs |0 EC 3.6.5.1 |2 NLM Chemicals |
| 700 | 1 | _ | |a Zhang, Liguo |b 1 |
| 700 | 1 | _ | |a Chen, Ying |b 2 |
| 700 | 1 | _ | |a Remke, Marc |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Shih, David |b 4 |
| 700 | 1 | _ | |a Lu, Fanghui |b 5 |
| 700 | 1 | _ | |a Wang, Haibo |b 6 |
| 700 | 1 | _ | |a Deng, Yaqi |b 7 |
| 700 | 1 | _ | |a Yu, Yang |b 8 |
| 700 | 1 | _ | |a Xia, Yong |b 9 |
| 700 | 1 | _ | |a Wu, Xiaochong |b 10 |
| 700 | 1 | _ | |a Ramaswamy, Vijay |b 11 |
| 700 | 1 | _ | |a Hu, Tom |b 12 |
| 700 | 1 | _ | |a Wang, Fan |b 13 |
| 700 | 1 | _ | |a Zhou, Wenhao |b 14 |
| 700 | 1 | _ | |a Burns, Dennis K |b 15 |
| 700 | 1 | _ | |a Kim, Se Hoon |0 0000-0001-7516-7372 |b 16 |
| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 17 |u dkfz |
| 700 | 1 | _ | |a Pfister, Stefan |0 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |b 18 |u dkfz |
| 700 | 1 | _ | |a Weinstein, Lee S |b 19 |
| 700 | 1 | _ | |a Pomeroy, Scott L |b 20 |
| 700 | 1 | _ | |a Gilbertson, Richard J |b 21 |
| 700 | 1 | _ | |a Rubin, Joshua B |b 22 |
| 700 | 1 | _ | |a Hou, Yiping |b 23 |
| 700 | 1 | _ | |a Wechsler-Reya, Robert |b 24 |
| 700 | 1 | _ | |a Taylor, Michael D |b 25 |
| 700 | 1 | _ | |a Lu, Q Richard |b 26 |
| 773 | _ | _ | |a 10.1038/nm.3666 |g Vol. 20, no. 9, p. 1035 - 1042 |0 PERI:(DE-600)1484517-9 |n 9 |p 1035 - 1042 |t Nature medicine |v 20 |y 2014 |x 1546-170X |
| 909 | C | O | |o oai:inrepo02.dkfz.de:120198 |p VDB |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 17 |6 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 18 |6 P:(DE-He78)f746aa965c4e1af518b016de3aaff5d9 |
| 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 2014 |
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