气候变化领域集成服务门户(CCPortal): The harsh microenvironment in early breast cancer selects for a Warburg phenotype

CCPortal

DOI	10.1073/PNAS.2011342118
	The harsh microenvironment in early breast cancer selects for a Warburg phenotype
	Damaghi M.; West J.; Robertson-Tessi M.; Xu L.; Ferrall-Fairbanks M.C.; Stewart P.A.; Persi E.; Fridley B.L.; Altrock P.M.; Gatenby R.A.; Sims P.A.; Anderson A.R.A.; Gillies R.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	The harsh microenvironment of ductal carcinoma in situ (DCIS) exerts strong evolutionary selection pressures on cancer cells. We hypothesize that the poor metabolic conditions near the ductal center foment the emergence of a Warburg Effect (WE) phenotype, wherein cells rapidly ferment glucose to lactic acid, even in normoxia. To test this hypothesis, we subjected low-glycolytic breast cancer cells to different microenvironmental selection pressures using combinations of hypoxia, acidosis, low glucose, and starvation for many months and isolated single clones for metabolic and transcriptomic profiling. The two harshest conditions selected for constitutively expressed WE phenotypes. RNA sequencing analysis of WE clones identified the transcription factor KLF4 as potential inducer of the WE phenotype. In stained DCIS samples, KLF4 expression was enriched in the area with the harshest microenvironmental conditions. We simulated in vivo DCIS phenotypic evolution using a mathematical model calibrated from the in vitro results. The WE phenotype emerged in the poor metabolic conditions near the necrotic core. We propose that harsh microenvironments within DCIS select for a WE phenotype through constitutive transcriptional reprogramming, thus conferring a survival advantage and facilitating further growth and invasion. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Adaptation; Clonal selection; DCIS; Tumor evolution; Warburg Effect
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/181006
作者单位	Department of Cancer Physiology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States; Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, United States; Department of Integrated Mathematical Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States; Biostatistics and Bioinformatics Shared Resource, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States; National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, United States; Department of System Biology, Columbia University Irving Medical Center, New York, NY 10032, United States; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, United States
推荐引用方式 GB/T 7714	Damaghi M.,West J.,Robertson-Tessi M.,et al. The harsh microenvironment in early breast cancer selects for a Warburg phenotype[J],2021,118(3).
APA	Damaghi M..,West J..,Robertson-Tessi M..,Xu L..,Ferrall-Fairbanks M.C..,...&Gillies R.J..(2021).The harsh microenvironment in early breast cancer selects for a Warburg phenotype.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Damaghi M.,et al."The harsh microenvironment in early breast cancer selects for a Warburg phenotype".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).