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PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype. Nat Commun. 2015 Dec 3;6:10068

发布时间:2016年01月25日

Nature Communications 2015 Dec 3;6:10068. doi: 10.1038/ncomms10068.

PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype.

Duan S1, Yuan G1, Liu X2, Ren R1,3,4, Li J2, Zhang W5, Wu J6, Xu X1, Fu L1, Li Y1, Yang J1, Zhang W1, Bai R3,4, Yi F7, Suzuki K6,8, Gao H9, Esteban CR6, Zhang C10, Izpisua Belmonte JC6, Chen Z11, Wang X10, Jiang T10, Qu J4, Tang F2,12,13,14, Liu GH1,3,10,13.

Abstract  

PTEN is a tumour suppressor frequently mutated in many types of cancers. Here we show that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells (NSCs), but not mesenchymal stem cells. PTEN-deficient NSCs display neoplasm-associated metabolic and gene expression profiles and generate intracranial tumours in immunodeficient mice. PTEN is localized to the nucleus in NSCs, binds to the PAX7 promoter through association with cAMP responsive element binding protein 1 (CREB)/CREB binding protein (CBP) and inhibits PAX7 transcription. PTEN deficiency leads to the upregulation of PAX7, which in turn promotes oncogenic transformation of NSCs and instates 'aggressiveness' in human glioblastoma stem cells. In a large clinical database, we find increased PAX7 levels in PTEN-deficient glioblastoma. Furthermore, we identify that mitomycin C selectively triggers apoptosis in NSCs with PTEN deficiency. Together, we uncover a potential mechanism of how PTEN safeguards NSCs, and establish a cellular platform to identify factors involved in NSC transformation, potentially permitting personalized treatment of glioblastoma.

相关报道:http://www.ibp.cas.cn/kyjz/zxdt/201512/t20151203_4487331.html

文章链接:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686761/

 

 

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