Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells

被引：245

作者：

Basu-Roy, Upal ^{[1
]}

Bayin, N. Sumru ^{[2
]}

Rattanakorn, Kirk ^{[1
]}

Han, Eugenia ^{[1
,3
]}

Placantonakis, Dimitris G. ^{[2
]}

Mansukhani, Alka ^{[1
]}

Basilico, Claudio ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Neurosurg, New York, NY 10016 USA

[3] NYU, Sch Med, Dept Pediat, NYU Canc Inst, New York, NY 10016 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

ORGAN SIZE CONTROL; SIGNALING PATHWAY; TISSUE REGENERATION; MOUSE MODEL; GROWTH; TAZ; YAP; PROLIFERATION; OSTEOSARCOMA; INHIBITION;

D O I：

10.1038/ncomms7411

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The repressive Hippo pathway has a profound tumour suppressive role in cancer by restraining the growth-promoting function of the transcriptional coactivator, YAP. We previously showed that the stem cell transcription factor Sox2 maintains cancer stem cells (CSCs) in osteosarcomas. We now report that in these tumours, Sox2 antagonizes the Hippo pathway by direct repression of two Hippo activators, Nf2 (Merlin) and WWC1 (Kibra), leading to exaggerated YAP function. Repression of Nf2, WWC1 and high YAP expression marks the CSC fraction of the tumor population, while the more differentiated fraction has high Nf2, high WWC1 and reduced YAP expression. YAP depletion sharply reduces CSCs and tumorigenicity of osteosarcomas. Thus, Sox2 interferes with the tumour-suppressive Hippo pathway to maintain CSCs in osteosarcomas. This Sox2-Hippo axis is conserved in other Sox2-dependent cancers such as glioblastomas. Disruption of YAP transcriptional activity could be a therapeutic strategy for Sox2-dependent tumours.

引用

页数：14

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