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dc.contributor.authorMei, Yang
dc.contributor.authorWang, Zhanxiang
dc.contributor.authorZhang, Lei
dc.contributor.authorZhang, Yiru
dc.contributor.authorLi, Xiaoyu
dc.contributor.authorLiu, Huihui
dc.contributor.authorYe, Jing
dc.contributor.authorYou, Han
dc.contributor.author尤涵
dc.date.accessioned2013-04-19T01:56:04Z
dc.date.available2013-04-19T01:56:04Z
dc.date.issued2012-03-27
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2012,109913):4898-4903zh_CN
dc.identifier.issn0027-8424
dc.identifier.urihttp://dx.doi.org/10.1073/pnas.1119535109
dc.identifier.uriWOS:000302164200042
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/15992
dc.description.abstractNeuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial early event in neuroblastoma pathogenesis is arrested differentiation of neuroblasts at various stages. Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation of neuroblastoma cells. However, the signaling pathways that are involved in this process remain largely unknown. Here, we report that inhibition of endogenous FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct its basal mRNA expression as well as its induction upon serum deprivation. Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic expression of PDGFRA abolished the blockage of neuroblastoma differentiation by FOXOs inhibition. These findings define the FOXO-PDGFRA axis as crucial mechanistic components that govern TPA-induced neuroblastoma differentiation.zh_CN
dc.description.sponsorshipNational Basic Research Program of China 973 Program [2009CB522202]; National Natural Science Foundation of China [31071195]; Ministry of Education of China [B06016]zh_CN
dc.language.isoenzh_CN
dc.publisherNATL ACAD SCIENCESzh_CN
dc.subjectINDUCED NEURONAL DIFFERENTIATIONzh_CN
dc.subjectFOXO3A-DEPENDENT REGULATIONzh_CN
dc.subjectRHO GTPASESzh_CN
dc.subjectCELLSzh_CN
dc.subjectACTIVATIONzh_CN
dc.subjectSURVIVALzh_CN
dc.subjectPATHWAYzh_CN
dc.subjectALPHAzh_CN
dc.titleRegulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRAzh_CN
dc.typeArticlezh_CN


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