气候变化领域集成服务门户(CCPortal): Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis

CCPortal

DOI	10.1126/science.aay0939
	Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis
	Ebright R.Y.; Lee S.; Wittner B.S.; Niederhoffer K.L.; Nicholson B.T.; Bardia A.; Truesdell S.; Wiley D.F.; Wesley B.; Li S.; Mai A.; Aceto N.; Vincent-Jordan N.; Szabolcs A.; Chirn B.; Kreuzer J.; Comaills V.; Kalinich M.; Haas W.; Ting D.T.; Toner M.; Vasudevan S.; Haber D.A.; Maheswaran S.; Micalizzi D.S.
发表日期	2020
ISSN	0036-8075
起始页码	1468
结束页码	1473
卷号	367 期号:6485
英文摘要	Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset of these cells generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in CTCs from breast cancer patients to identify genes that promote distant metastasis in mice. Genes coding for ribosomal proteins and regulators of translation were enriched in this screen. Overexpression of RPL15, which encodes a component of the large ribosomal subunit, increased metastatic growth in multiple organs and selectively enhanced translation of other ribosomal proteins and cell cycle regulators. RNA sequencing of freshly isolated CTCs from breast cancer patients revealed a subset with strong ribosome and protein synthesis signatures; these CTCs expressed proliferation and epithelial markers and correlated with poor clinical outcome. Therapies targeting this aggressive subset of CTCs may merit exploration as potential suppressors of metastatic progression. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	CRISPR associated protein epidermal growth factor receptor 2 Ki 67 antigen ribosome protein ribosome RNA transcription factor E2F ribosome protein cancer cell gene expression genetic engineering protein RNA tumor animal experiment animal model animal tissue Article biogenesis bioluminescence breast cancer cell cycle progression cell cycle regulation cell proliferation circulating tumor cell controlled study enzyme activation epithelial mesenchymal transition gene expression profiling genetic transcription human human cell lung metastasis metastasis microfluidics mouse nonhuman overall survival phenotype priority journal progression free survival promoter region protein expression protein processing protein synthesis proteomics RNA sequence transcription regulation animal breast tumor cancer transplantation CRISPR Cas system female gene expression regulation genetics pathology sequence analysis tumor cell line tumor embolism Mus Animals Breast Neoplasms Cell Line, Tumor CRISPR-Cas Systems Female Gene Expression Regulation, Neoplastic Humans Mice Neoplasm Metastasis Neoplasm Transplantation Neoplastic Cells, Circulating Ribosomal Proteins Sequence Analysis, RNA
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133595
推荐引用方式 GB/T 7714	Ebright R.Y.,Lee S.,Wittner B.S.,et al. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis[J]. Science,2020,367(6485).
APA	Ebright R.Y..,Lee S..,Wittner B.S..,Niederhoffer K.L..,Nicholson B.T..,...&Micalizzi D.S..(2020).Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.,367(6485).
MLA	Ebright R.Y.,et al."Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis".367.6485(2020).