Hwang Wei-Lun, Yang Muh-Hwa
a The Ph.D Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University , Taipei , Taiwan.
b Institute of Clinical Medicine, National Yang-Ming University , Taipei , Taiwan.
Cell Cycle. 2016 Oct 17;15(20):2697-703. doi: 10.1080/15384101.2016.1218101. Epub 2016 Aug 11.
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.
干细胞对称与不对称分裂之间的平衡调控着组织稳态，而这种平衡的失调会引发肿瘤形成。尽管Numb在正常干细胞中的许多功能已得到证实，但其在癌症干细胞中的作用相对尚不明确。我们最近证明，在结直肠癌干细胞中，Numb受到miR-146a-5p的抑制，这导致Wnt信号通路激活和模板DNA对称分裂。在此，我们证明PKH26标记的亚细胞灶富含诸如EEA1和RAB11等内体标记物。在结直肠癌干细胞中，PKH-26标记的囊泡在第一次有丝分裂时均等分离；相反，它们在亲代细胞或经历血清诱导分化的癌症干细胞中不均等分离。结直肠癌干细胞的PKH（明亮）子代具有干细胞表型，而PKH（暗淡）子代表现为分化细胞。miR-146a-5p调控的Numb控制着PKH26囊泡的分布。我们的结果表明Numb在结直肠癌干细胞分裂过程中控制亚细胞囊泡分离方面起着关键作用。
