| A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. | |
| | |
MedLine Citation:
|
PMID: 20371346 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Accumulating evidence implicates heterogeneity within cancer cell populations in the response to stressful exposures, including drug treatments. While modeling the acute response to various anticancer agents in drug-sensitive human tumor cell lines, we consistently detected a small subpopulation of reversibly "drug-tolerant" cells. These cells demonstrate >100-fold reduced drug sensitivity and maintain viability via engagement of IGF-1 receptor signaling and an altered chromatin state that requires the histone demethylase RBP2/KDM5A/Jarid1A. This drug-tolerant phenotype is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity in drug tolerance. The drug-tolerant subpopulation can be selectively ablated by treatment with IGF-1 receptor inhibitors or chromatin-modifying agents, potentially yielding a therapeutic opportunity. Together, these findings suggest that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures. |
| | |
Authors:
|
Sreenath V Sharma; Diana Y Lee; Bihua Li; Margaret P Quinlan; Fumiyuki Takahashi; Shyamala Maheswaran; Ultan McDermott; Nancy Azizian; Lee Zou; Michael A Fischbach; Kwok-Kin Wong; Kathleyn Brandstetter; Ben Wittner; Sridhar Ramaswamy; Marie Classon; Jeff Settleman |
Related Documents
:
|
2743306 - Proton-mediated liberation of aldophosphamide from a nontoxic prodrug: a strategy for t... 6615686 - Some tetracycline drugs suppress mitogen-stimulated lymphocyte growth but others do not. 21609756 - Doxorubicin and paclitaxel loaded microbubbles for ultrasound triggered drug delivery. 7444146 - Clinical correlations of drug sensitivity in the human tumor stem cell assay. 15211616 - Qt prolongation in anaesthetized guinea-pigs: an experimental approach for preliminary ... 15616666 - Update on antiobesity drugs. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cell Volume: 141 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2010 Apr |
Date Detail:
|
Created Date: 2010-04-07 Completed Date: 2010-04-22 Revised Date: 2011-07-27 |
Medline Journal Info:
|
Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
|
Languages: eng Pagination: 69-80 Citation Subset: IM |
Copyright Information:
|
Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Massachusetts General Hospital Cancer Center, 149 13th Street, Charlestown, MA 02129, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Line, Tumor Chromatin / metabolism, pathology DNA Damage Drug Resistance, Neoplasm* Histone Deacetylase Inhibitors / pharmacology Histone Demethylases / metabolism Humans Jumonji Domain-Containing Histone Demethylases / antagonists & inhibitors, genetics, metabolism Neoplasms / drug therapy*, metabolism, pathology* Receptor, IGF Type 1 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
P20 CA090578/CA/NCI NIH HHS; P50 CA090578-060008/CA/NCI NIH HHS; P50 CA090578-070008/CA/NCI NIH HHS; R01 CA142825-01/CA/NCI NIH HHS; R01CA115830/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Chromatin; 0/Histone Deacetylase Inhibitors; EC 1.14.11.-/Histone Demethylases; EC 1.14.11.-/Jumonji Domain-Containing Histone Demethylases; EC 1.5.-/KDM4A protein, human; EC 2.7.10.1/Receptor, IGF Type 1 |
| Comments/Corrections | |
Comment In:
|
Cell. 2010 Apr 2;141(1):18-20
[PMID:
20371339
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Matrix metalloproteinases: regulators of the tumor microenvironment.
Next Document: Persistent telomere damage induces bypass of mitosis and tetraploidy.