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Asymmetric cancer cell division regulated by AKT.

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.

SUBMITTER: Dey-Guha I

PROVIDER: S-EPMC3150943 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Asymmetric cancer cell division regulated by AKT.

Dey-Guha Ipsita I Wolfer Anita A Yeh Albert C AC G Albeck John J Darp Revati R Leon Eduardo E Wulfkuhle Julia J Petricoin Emanuel F EF Wittner Ben S BS Ramaswamy Sridhar S

Proceedings of the National Academy of Sciences of the United States of America 20110714 31

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 AK ...[more]

PMID: 21757645

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