Article: article from journal or magazin.
Asymmetric cancer cell division regulated by AKT.
Proceedings of the National Academy of Sciences of the United States of America
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
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.
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
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