Cited 101 times in
The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog−driven medulloblastoma
DC Field | Value | Language |
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dc.contributor.author | 김세훈 | - |
dc.date.accessioned | 2015-01-06T17:37:22Z | - |
dc.date.available | 2015-01-06T17:37:22Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/100323 | - |
dc.description.abstract | 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. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1035~1042 | - |
dc.relation.isPartOf | NATURE MEDICINE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Brain Neoplasms/metabolism* | - |
dc.subject.MESH | Cyclic AMP/metabolism | - |
dc.subject.MESH | GTP-Binding Protein alpha Subunits, Gs/genetics | - |
dc.subject.MESH | GTP-Binding Protein alpha Subunits, Gs/metabolism* | - |
dc.subject.MESH | Hedgehog Proteins/metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Medulloblastoma/metabolism* | - |
dc.subject.MESH | Neural Stem Cells/metabolism | - |
dc.subject.MESH | Signal Transduction | - |
dc.title | The G protein α subunit Gαs is a tumor suppressor in Sonic hedgehog−driven medulloblastoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학) | - |
dc.contributor.googleauthor | Xuelian He | - |
dc.contributor.googleauthor | Liguo Zhang | - |
dc.contributor.googleauthor | Ying Chen | - |
dc.contributor.googleauthor | Marc Remke | - |
dc.contributor.googleauthor | David Shih | - |
dc.contributor.googleauthor | Fanghui Lu | - |
dc.contributor.googleauthor | Haibo Wang | - |
dc.contributor.googleauthor | Yaqi Deng | - |
dc.contributor.googleauthor | Yang Yu | - |
dc.contributor.googleauthor | Yong Xia | - |
dc.contributor.googleauthor | Xiaochong Wu | - |
dc.contributor.googleauthor | Vijay Ramaswamy | - |
dc.contributor.googleauthor | Tom Hu | - |
dc.contributor.googleauthor | Fan Wang | - |
dc.contributor.googleauthor | Wenhao Zhou | - |
dc.contributor.googleauthor | Dennis K Burns | - |
dc.contributor.googleauthor | Se Hoon Kim | - |
dc.contributor.googleauthor | Marcel Kool | - |
dc.contributor.googleauthor | Stefan M Pfister | - |
dc.contributor.googleauthor | Lee S Weinstein | - |
dc.contributor.googleauthor | Scott L Pomeroy | - |
dc.contributor.googleauthor | Richard J Gilbertson | - |
dc.contributor.googleauthor | Joshua B Rubin | - |
dc.contributor.googleauthor | Yiping Hou | - |
dc.contributor.googleauthor | Robert Wechsler-Reya | - |
dc.contributor.googleauthor | Michael D Taylor | - |
dc.contributor.googleauthor | Q Richard Lu | - |
dc.identifier.doi | 10.1038/nm.3666 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00610 | - |
dc.relation.journalcode | J02296 | - |
dc.identifier.eissn | 1546-170X | - |
dc.identifier.pmid | 25150496 | - |
dc.identifier.url | http://www.nature.com/nm/journal/v20/n9/full/nm.3666.html | - |
dc.contributor.alternativeName | Kim, Se Hoon | - |
dc.contributor.affiliatedAuthor | Kim, Se Hoon | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 20 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 1035 | - |
dc.citation.endPage | 1042 | - |
dc.identifier.bibliographicCitation | NATURE MEDICINE, Vol.20(9) : 1035-1042, 2014 | - |
dc.identifier.rimsid | 57588 | - |
dc.type.rims | ART | - |
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