title: 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.
authors.affiliation: Centers for Cancer Research, Regenerative Medicine, Human Genetics Research, and Systems Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Dey-Guha
authors.forename: Anita
authors.initials: A
authors.lastname: Wolfer
authors.forename: Albert C
authors.initials: AC
authors.lastname: Yeh
authors.forename: John
authors.initials: J
authors.lastname: G Albeck
authors.forename: Revati
authors.initials: R
authors.lastname: Darp
authors.forename: Eduardo
authors.initials: E
authors.lastname: Leon
authors.forename: Julia
authors.initials: J
authors.lastname: Wulfkuhle
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Ben S
authors.initials: BS
authors.lastname: Wittner
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D015394:Molecular Structure; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D008164:Luminescent Proteins; C548887:MK 2206; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt