title: Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity.
abstract: 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. 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'.
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Tse-Chun
authors: TC
authors: Kuo
authors: Chun-Ting
authors: CT
authors: Chen
authors: Desiree
authors: D
authors: Baron
authors: Tamer T
authors: TT
authors: Onder
authors: Sabine
authors: S
authors: Loewer
authors: Sandra
authors: S
authors: Almeida
authors: Cara M
authors: CM
authors: Weismann
authors: Ping
authors: P
authors: Xu
authors: Jean-Marie
authors: JM
authors: Houghton
authors: Fen-Biao
authors: FB
authors: Gao
authors: George Q
authors: GQ
authors: Daley
authors: Stephen
authors: S
authors: Doxsey
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D065150:Cellular Reprogramming; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006367:HeLa Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015388:Organelles / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C505378:Cep55 protein, human; D002868:Chromosomal Proteins, Non-Histone; D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C056608:caltractin