Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity
Onder, Tamer T.
Weismann, Cara M.
Daley, George Q.
Doxsey, Stephen J.
UMass Chan AffiliationsDepartment of Medicine, Division of Gastroenterology
Department of Neurology
Program in Molecular Medicine
Document TypeJournal Article
Cell Cycle Proteins
Cell Transformation, Neoplastic
Chromosomal Proteins, Non-Histone
Embryonic Stem Cells
Induced Pluripotent Stem Cells
Neoplastic Stem Cells
Recombinant Fusion Proteins
Cellular and Molecular Physiology
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AbstractThe 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. MB(d) 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. MB(d) 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'.
SourceNat Cell Biol. 2011 Sep 11;13(10):1214-23. doi: 10.1038/ncb2332. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/37739
Co-author Tse-Chun Kuo is a student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
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