The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog-driven Medulloblastoma

DSpace/Manakin Repository

The G-protein Alpha Subunit Gsα Is A Tumor Suppressor In Sonic Hedgehog-driven Medulloblastoma

Show simple item record

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

Files in this item

Files Size Format View
4334261.pdf 1.723Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters