气候变化领域集成服务门户(CCPortal): SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice

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DOI	10.1073/pnas.2017115118
	SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice
	Moncho-Amor V.; Chakravarty P.; Galichet C.; Matheu A.; Lovell-Badge R.; Rizzoti K.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	P27, a cell cycle inhibitor, is also able to drive repression of Sox2. This interaction plays a crucial role during development of p27−/− pituitary tumors because loss of one copy of Sox2 impairs tumorigenesis [H. Li et al., Cell Stem Cell 11, 845–852 (2012)]. However, SOX2 is expressed in both endocrine and stem cells (SCs), and its contribution to tumorigenesis in either cell type is unknown. We have thus explored the cellular origin and mechanisms underlying endocrine tumorigenesis in p27−/− pituitaries. We found that pituitary hyperplasia is associated with reduced cellular differentiation, in parallel with increased levels of SOX2 in stem and endocrine cells. Using conditional loss-of-function and lineage tracing approaches, we show that SOX2 is required cell autonomously in p27−/− endocrine cells for these to give rise to tumors, and in SCs for promotion of tumorigenesis. This is supported by studies deleting the Sox2 regulatory region 2 (Srr2), the target of P27 repressive action. Single cell transcriptomic analysis further reveals that activation of a SOX2-dependent MAPK pathway in SCs is important for tumorigenesis. Altogether, our data highlight different aspects of the role of SOX2 following loss of p27, according to cellular context, and uncover an unexpected SOX2-dependent tumor-promoting role for SCs. Our results imply that targeting SCs, in addition to tumor cells, may represent an efficient antitumoral strategy in certain contexts. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Pituitary \| stem cell \| tumorigenesis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180664
作者单位	Laboratory of Stem Cell Biology and Developmental Genetics, Francis Crick Institute, London, NW1 1AT, United Kingdom; Bioinformatics Core, Francis Crick Institute, London, NW1 1AT, United Kingdom; Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, E-20014, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid, 28029, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, 48013, Spain
推荐引用方式 GB/T 7714	Moncho-Amor V.,Chakravarty P.,Galichet C.,et al. SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice[J],2021,118(7).
APA	Moncho-Amor V.,Chakravarty P.,Galichet C.,Matheu A.,Lovell-Badge R.,&Rizzoti K..(2021).SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Moncho-Amor V.,et al."SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in p27-null mice".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).