Asymmetric cancer cell division regulated by AKT.

Details

Serval ID
serval:BIB_BA80EEE2F3A0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Asymmetric cancer cell division regulated by AKT.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Dey-Guha I., Wolfer A., Yeh A.C., Albeck J.G., Darp R., Leon E., Wulfkuhle J., Petricoin E.F., Wittner B.S., Ramaswamy S.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2011
Volume
108
Number
31
Pages
12845-12850
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.Publication Status: ppublish
Abstract
Human tumors often contain slowly proliferating cancer cells that resist treatment, but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating "G0-like" progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small-molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur.
Keywords
Blotting, Western, Breast Neoplasms/genetics, Breast Neoplasms/metabolism, Cell Division, Cell Line, Tumor, Cell Survival/drug effects, Dose-Response Relationship, Drug, Female, G0 Phase, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, HCT116 Cells, Heterocyclic Compounds, 3-Ring/chemistry, Heterocyclic Compounds, 3-Ring/pharmacology, Humans, Luminescent Proteins/genetics, Luminescent Proteins/metabolism, Microscopy, Confocal, Models, Biological, Molecular Structure, Neoplasms/genetics, Neoplasms/metabolism, Oligonucleotide Array Sequence Analysis, Proto-Oncogene Proteins c-akt/antagonists & inhibitors, Proto-Oncogene Proteins c-akt/genetics, Reactive Oxygen Species/metabolism, Signal Transduction/drug effects, Time Factors
Pubmed
Web of science
Open Access
Yes
Create date
07/02/2012 14:11
Last modification date
20/08/2019 15:28
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