气候变化领域集成服务门户(CCPortal): MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex

CCPortal

DOI	10.1073/pnas.2024824118
	MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex
	Llabata P.; Torres-Diz M.; Gomez A.; Tomas-Daza L.; Romero O.A.; Grego-Bessa J.; Llinas-Arias P.; Valencia A.; Esteller M.; Javierre B.M.; Zhang X.; Sanchez-Cespedes M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:37
英文摘要	The MYC axis is disrupted in cancer, predominantly through activation of the MYC family oncogenes but also through inactivation of the MYC partner MAX or of the MAX partner MGA. MGA and MAX are also members of the polycomb repressive complex, ncPRC1.6. Here, we use genetically modified MAX-deficient small-cell lung cancer (SCLC) cells and carry out genome-wide and proteomics analyses to study the tumor suppressor function of MAX. We find that MAX mutant SCLCs have ASCL1 or NEUROD1 or combined ASCL1/NEUROD1 characteristics and lack MYC transcriptional activity. MAX restitution triggers prodifferentiation expression profiles that shift when MAX and oncogenic MYC are coexpressed. Although ncPRC1.6 can be formed, the lack of MAX restricts global MGA occupancy, selectively driving its recruitment toward E2F6-binding motifs. Conversely, MAX restitution enhances MGA occupancy to repress genes involved in different functions, including stem cell and DNA repair/replication. Collectively, these findings reveal that MAX mutant SCLCs have either ASCL1 or NEUROD1 or combined characteristics and are MYC independent and exhibit deficient ncPRC1.6-mediated gene repression. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	MAX; MGA; ncPRC1.6; SCLC; Tumor suppressor
语种	英语
scopus关键词	BMI1 protein; Max protein; MGA protein; Myc protein; nancanonical polycomb repressive complex 1; neurogenic differentiation factor; polycomb group protein; transcription factor Mash1; unclassified drug; ASCL1 protein, human; basic helix loop helix leucine zipper transcription factor; basic helix loop helix transcription factor; cell cycle protein; MAX protein, human; MGA protein, human; Myc protein; MYC protein, human; NEUROD1 protein, human; polycomb group protein; PRC1 protein, human; tumor marker; animal cell; animal experiment; animal model; animal tissue; Article; controlled study; DNA repair; DNA replication; enzyme activation; gene repression; human; mouse; nonhuman; protein binding; protein expression; protein function; protein protein interaction; proteomics; RNA sequencing; small cell lung cancer; apoptosis; cell proliferation; gene expression regulation; genetics; lung tumor; metabolism; pathology; promoter region; small cell lung cancer; tumor cell culture; Apoptosis; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Cell Cycle Proteins; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Polycomb-Group Proteins; Promoter Regions, Genetic; Proto-Oncogene Proteins c-myc; Small Cell Lung Carcinoma; Tumor Cells, Cultured
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/251020
作者单位	Cancer Genetics Group, Josep Carreras Leukaemia Research Institute, Barcelona, 08916, Spain; Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain; Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, 08035, Spain; 3D Chromatin Organization Group, Josep Carreras Leukaemia Research Institute, Barcelona, 08916, Spain; Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute, Barcelona, 08916, Spain; Computational Biology Life Sciences Group, Barcelona Supercomputing Centre, Barcelona, 08034, Spain; Centro de Investigacion Biomedica en Red Cancer, Madrid, 28029, Spain; Institucio Catalana de Recerca i Estudis Avançats, Barcelona, 08010, Spain; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona, Barcelona, 08907, Spain; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, United States
推荐引用方式 GB/T 7714	Llabata P.,Torres-Diz M.,Gomez A.,et al. MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex[J],2021,118(37).
APA	Llabata P..,Torres-Diz M..,Gomez A..,Tomas-Daza L..,Romero O.A..,...&Sanchez-Cespedes M..(2021).MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex.Proceedings of the National Academy of Sciences of the United States of America,118(37).
MLA	Llabata P.,et al."MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex".Proceedings of the National Academy of Sciences of the United States of America 118.37(2021).