title: Numb is involved in the non-random segregation of subcellular vesicles in colorectal cancer stem cells.
abstract: The balance between the symmetric and asymmetric division of stem cells governs tissue homeostasis, and the deregulation of this balance initiates tumor formation. Although many functions of Numb have been demonstrated in normal stem cells, the role of Numb in cancer stem cells is relatively unclear. We recently demonstrated that in colorectal cancer stem cells, Numb was suppressed by miR-146a-5p, which resulted in the activation of the Wnt signaling pathway and symmetric template DNA division. Here, we demonstrate that the PKH26-labeled subcellular foci are enriched for endosomal markers such as EEA1 and RAB11. In colorectal cancer stem cells, the PKH-26-labeled vesicles are segregated equally at the first mitotic division; in contrast, they are unequally segregated in parental cells or in cancer stem cells undergoing serum-induced differentiation. The PKH(Bright) progeny of colorectal cancer stem cells harbors a stem cell phenotype, whereas the PKH(Dim) progeny behaves as the differentiating cells. The miR-146a-5p-regulated Numb controls the distribution of PKH26 vesicles. Our results suggest a critical role of Numb in controlling the segregation of subcellular vesicles during division of colorectal cancer stem cells.
authors: a The Ph.D Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University , Taipei , Taiwan.
authors: Wei-Lun
authors: WL
authors: Hwang
authors: b Institute of Clinical Medicine, National Yang-Ming University , Taipei , Taiwan.|c Genome Research Center, National Yang-Ming University , Taipei , Taiwan.|d Division of Medical Oncology , Department of Oncology , Taipei Veterans General Hospital , Taipei , Taiwan.|e Genomics Research Center, Academia Sinica , Taipei , Taiwan.
authors: Muh-Hwa
authors: MH
authors: Yang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D019070:Cell Lineage; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins
keywords: Asymmetric Cell Division; Cancer Stem Cell; Colorectal Cancer; Numb; miRNA