Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity

被引：185

作者：

Kuo, Tse-Chun ^{[1
]}

Chen, Chun-Ting ^{[1
]}

Baron, Desiree ^{[1
]}

Onder, Tamer T. ^{[2
,3
,4
,5
,6
]}

Loewer, Sabine ^{[2
,3
,4
,5
,6
]}

Almeida, Sandra ^{[7
]}

Weismann, Cara M. ^{[1
,7
]}

Xu, Ping ^{[1
]}

Houghton, Jean-Marie ^{[8
]}

Gao, Fen-Biao ^{[7
]}

Daley, George Q. ^{[2
,3
,4
,5
,6
,9
]}

Doxsey, Stephen ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA

[2] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[3] Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

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

[7] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA

[8] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA

[9] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE CELL BIOLOGY | 2011年 / 13卷 / 10期

基金：

美国国家卫生研究院;

关键词：

STEM-CELLS; NEURAL PROGENITORS; ASYMMETRIC INHERITANCE; MEMBRANE; CYTOKINESIS; CENTROSOME; DISEASE; DEGRADATION; DIVISION; LITHIUM;

D O I：

10.1038/ncb2332

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The midbody is a singular organelle formed between daughter cells during cytokinesis and required for their final separation. Midbodies persist in cells long after division as midbody derivatives (MB(d)s), but their fate is unclear. Here we show that MB(d)s are inherited asymmetrically by the daughter cell with the older centrosome. They selectively accumulate in stem cells, induced pluripotent stem cells and potential cancer 'stem cells' in vivo and in vitro. MBd loss accompanies stem-cell differentiation, and involves autophagic degradation mediated by binding of the autophagic receptor NBR1 to the midbody protein CEP55. Differentiating cells and normal dividing cells do not accumulate MB(d)s and possess high autophagic activity. Stem cells and cancer cells accumulate MB(d)s by evading autophagosome encapsulation and exhibit low autophagic activity. MBd enrichment enhances reprogramming to induced pluripotent stem cells and increases the in vitro tumorigenicity of cancer cells. These results indicate unexpected roles for MB(d)s in stem cells and cancer 'stem cells'.

引用

页码：1214 / U110

页数：19

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