Asymmetric cancer cell division regulated by AKT

被引：95

作者：

Dey-Guha, Ipsita ^{[1
,2
,3
,4
,5
]}

Wolfer, Anita ^{[1
,2
,3
,4
,5
]}

Yeh, Albert C. ^{[5
]}

Albeck, John G. ^{[5
]}

Darp, Revati ^{[1
,2
,3
,4
]}

Leon, Eduardo ^{[1
,2
,3
,4
]}

Wulfkuhle, Julia ^{[6
]}

Petricoin, Emanuel F., III ^{[6
]}

Wittner, Ben S. ^{[1
,2
,3
,4
,5
]}

Ramaswamy, Sridhar ^{[1
,2
,3
,4
,5
,7
,8
,9
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Boston, MA 02115 USA

[6] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA

[7] Broad Inst Harvard, Cambridge, MA 02142 USA

[8] MIT, Cambridge, MA 02142 USA

[9] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 31期

基金：

瑞士国家科学基金会;

关键词：

OXIDATIVE STRESS; SELF-RENEWAL; STEM-CELLS; ACTIVATION; INHIBITION; QUIESCENT; EFFICACY; STATE;

D O I：

10.1073/pnas.1109632108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：12845 / 12850

页数：6

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