Asymmetric cancer cell division regulated by AKT
- 14 July 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (31), 12845-12850
- https://doi.org/10.1073/pnas.1109632108
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.This publication has 35 references indexed in Scilit:
- Asymmetric cell division: recent developments and their implications for tumour biologyNature Reviews Molecular Cell Biology, 2010
- MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted DrugsIn vitroandIn vivoMolecular Cancer Therapeutics, 2010
- A Temporarily Distinct Subpopulation of Slow-Cycling Melanoma Cells Is Required for Continuous Tumor GrowthCell, 2010
- A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell SubpopulationsCell, 2010
- MYC regulation of a “poor-prognosis” metastatic cancer cell stateProceedings of the National Academy of Sciences of the United States of America, 2010
- Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancerGenes & Development, 2009
- Mst1-FoxO Signaling Protects Naïve T Lymphocytes from Cellular Oxidative Stress in MicePLOS ONE, 2009
- Inhibition of Phosphorylation of BAD and Raf-1 by Akt Sensitizes Human Ovarian Cancer Cells to PaclitaxelJournal of Biological Chemistry, 2002
- Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion frontOncogene, 2001
- Redox state is a central modulator of the balance between self-renewal and differentiation in a dividing glial precursor cellProceedings of the National Academy of Sciences of the United States of America, 2000