Asymmetric cancer cell division regulated by AKT

Ipsita Dey-Guha, Anita Wolfer, Albert C. Yeh, John Albeck, Revati Darp, Eduardo Leon, Julia Wulfkuhle, Emanuel F. Petricoin, Ben S. Wittner, Sridhar Ramaswamy

Research output: Contribution to journalArticle

73 Citations (Scopus)

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 smallmolecule 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.

Original languageEnglish (US)
Pages (from-to)12845-12850
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011
Externally publishedYes

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Asymmetric Cell Division
Neoplasms
Telophase
Mitosis
Phosphotransferases
Breast Neoplasms
Drug Therapy
Therapeutics

Keywords

  • Cell signaling
  • Drug resistance
  • Epigenetics
  • Quiescence

ASJC Scopus subject areas

  • General

Cite this

Asymmetric cancer cell division regulated by AKT. / Dey-Guha, Ipsita; Wolfer, Anita; Yeh, Albert C.; Albeck, John; Darp, Revati; Leon, Eduardo; Wulfkuhle, Julia; Petricoin, Emanuel F.; Wittner, Ben S.; Ramaswamy, Sridhar.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 31, 02.08.2011, p. 12845-12850.

Research output: Contribution to journalArticle

Dey-Guha, I, Wolfer, A, Yeh, AC, Albeck, J, Darp, R, Leon, E, Wulfkuhle, J, Petricoin, EF, Wittner, BS & Ramaswamy, S 2011, 'Asymmetric cancer cell division regulated by AKT', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 31, pp. 12845-12850. https://doi.org/10.1073/pnas.1109632108
Dey-Guha, Ipsita ; Wolfer, Anita ; Yeh, Albert C. ; Albeck, John ; Darp, Revati ; Leon, Eduardo ; Wulfkuhle, Julia ; Petricoin, Emanuel F. ; Wittner, Ben S. ; Ramaswamy, Sridhar. / Asymmetric cancer cell division regulated by AKT. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 31. pp. 12845-12850.
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