气候变化领域集成服务门户(CCPortal): Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis

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DOI	10.1073/pnas.2026507118
	Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis
	Mrouj K.; Andrés-Sánchez N.; Dubra G.; Singh P.; Sobecki M.; Chahar D.; Al Ghoul E.; Aznar A.B.; Prieto S.; Pirot N.; Bernex F.; Bordignon B.; Hassen-Khodja C.; Villalba M.; Krasinska L.; Fisher D.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial–mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment. This facilitates multiple steps of carcinogenesis and drug resistance, yet may render cancer cells more susceptible to antitumor immune responses. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cancer; Genetically modified mice; Ki-67; Transcription
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/180345
作者单位	Institut de Génétique Moléculaire de Montpellier, CNRS, INSERM, University of Montpellier, Montpellier, 34293, France; Equipe Labellisée Ligue 2018, Ligue Nationale Contre le Cancer, Paris, 75013, France; Institut de Recherche en Cancérologie de Montpellier, Institut du Cancer de Montpellier, INSERM, University of Montpellier, Montpellier, 34090, France; BioCampus, Le Réseau d’Histologie Expérimentale de Montpellier, CNRS, INSERM, University of Montpellier, Montpellier, 34090, France; BioCampus, Montpellier Ressources Imagerie, CNRS, INSERM, University of Montpellier, Montpellier, 34090, France; Institute of Regenerative Medicine and Biotherapies, INSERM, University of Montpellier, Montpellier, 34295, France
推荐引用方式 GB/T 7714	Mrouj K.,Andrés-Sánchez N.,Dubra G.,et al. Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis[J],2021,118(10).
APA	Mrouj K..,Andrés-Sánchez N..,Dubra G..,Singh P..,Sobecki M..,...&Fisher D..(2021).Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Mrouj K.,et al."Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).