dc.contributor.author | He, Xuelian | en_US |
dc.contributor.author | Zhang, Liguo | en_US |
dc.contributor.author | Chen, Ying | en_US |
dc.contributor.author | Remke, Marc | en_US |
dc.contributor.author | Shih, David | en_US |
dc.contributor.author | Lu, Fanghui | en_US |
dc.contributor.author | Wang, Haibo | en_US |
dc.contributor.author | Deng, Yaqi | en_US |
dc.contributor.author | Yu, Yang | en_US |
dc.contributor.author | Xia, Yong | en_US |
dc.contributor.author | Wu, Xiaochong | en_US |
dc.contributor.author | Ramaswamy, Vijay | en_US |
dc.contributor.author | Hu, Tom | en_US |
dc.contributor.author | Wang, Fan | en_US |
dc.contributor.author | Zhou, Wenhao | en_US |
dc.contributor.author | Burns, Dennis K. | en_US |
dc.contributor.author | Kim, Se Hoon | en_US |
dc.contributor.author | Kool, Marcel | en_US |
dc.contributor.author | Pfister, Stefan M. | en_US |
dc.contributor.author | Weinstein, Lee S. | en_US |
dc.contributor.author | Pomeroy, Scott L. | en_US |
dc.contributor.author | Gilbertson, Richard J. | en_US |
dc.contributor.author | Rubin, Joshua B. | en_US |
dc.contributor.author | Hou, Yiping | en_US |
dc.contributor.author | Wechsler-Reya, Robert | en_US |
dc.contributor.author | Taylor, Michael D. | en_US |
dc.contributor.author | Lu, Q. Richard | en_US |
dc.date.accessioned | 2015-04-01T15:30:55Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | He, X., L. Zhang, Y. Chen, M. Remke, D. Shih, F. Lu, H. Wang, et al. 2014. “The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog-driven Medulloblastoma.” Nature medicine 20 (9): 1035-1042. doi:10.1038/nm.3666. http://dx.doi.org/10.1038/nm.3666. | en |
dc.identifier.issn | 1078-8956 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351378 | |
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 Gsα, as a potent tumor suppressor gene that defines a subset of aggressive Sonic Hedgehog (Shh)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically-distinct progenitors is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. Gsα 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 of a Gsα effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas mutants. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for Gsα that acts as a molecular link across Shh-group medulloblastomas of disparate cellular and anatomical origins, illuminating G-protein modulation as a potential therapeutic avenue. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/nm.3666 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334261/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | medulloblastoma | en |
dc.subject | G-protein | en |
dc.subject | cAMP | en |
dc.subject | GPCR | en |
dc.subject | cell lineage | en |
dc.subject | sonic hedgehog signaling | en |
dc.subject | cilia | en |
dc.subject | cellular origins | en |
dc.title | The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog-driven Medulloblastoma | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature medicine | en |
dash.depositing.author | Pomeroy, Scott L. | en_US |
dc.date.available | 2015-04-01T15:30:55Z | |
dc.identifier.doi | 10.1038/nm.3666 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Pomeroy, Scott | |