Physiological β-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinomaReport as inadecuate




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BMC Cell Biology

, 14:44

Cell differentiation and proliferation

Abstract

BackgroundA few reports suggested that low levels of Wnt signaling might drive cell reprogramming, but these studies could not establish a clear relationship between Wnt signaling and self-renewal networks. There are ongoing debates as to whether and how the Wnt-β-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological β-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of β-catenin and wild-type expression of p53, which provided a possibility to study regulatory mechanism of stemness networks induced by physiological levels of Wnt signaling in these cells.

ResultsIntroduction of increased β-catenin signaling, haploid expression of β-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt-β-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous β-catenin expression. HONE1 hybrid cells displayed stem cell-like properties, including enhancement of CD24 and CD44 populations and generation of spheres that were not observed in parental HONE1 cells. Signaling cascades were detected in HONE1 hybrid cells, including activation of p53- and RB1-mediated tumor suppressor pathways, up-regulation of Nanog-, Oct4-, Sox2-, and Klf4-mediated pluripotency networks, and altered E-cadherin expression in both in vitro and in vivo assays. qPCR array analyses further revealed interactions of physiological Wnt-β-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-β, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using β-catenin shRNA inhibitory assays, a dominant role for β-catenin in these cellular network activities was observed. The expression of cell surface markers such as CD9, CD24, CD44, CD90, and CD133 in generated spheres was progressively up-regulated compared to HONE1 hybrid cells. Thirty-four up-regulated components of the Wnt pathway were identified in these spheres.

ConclusionsWnt-β-catenin signaling regulates self-renewal networks and plays a central role in the control of pluripotency genes, tumor suppressive pathways and expression of cancer stem cell markers. This current study provides a novel platform to investigate the interaction of physiological Wnt-β-catenin signaling with stemness transition networks.

KeywordsPhysiological Wnt-β-catenin signaling Nasopharyngeal carcinoma Self-renewal network Chromosome 3 transfer Stemness transition Tumor suppressor genes Cancer stem cell markers AbbreviationsBIOBromoindirubin-3’-oxime

CSCCancer stem cells

DMEMDulbecco’s modified eagle medium

EMTEpithelial-mesenchymal transition

FGFFibroblast growth factor

MHCMicrocell hybrid cell

MTT3-4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide

NPCNasopharyngeal carcinoma

ShRNAShort hairpin RNA

TGF-βTransforming growth factor-β

TSTumor segregants

TSGTumor suppressor gene.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-14-44 contains supplementary material, which is available to authorized users.

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Author: Yue Cheng - Arthur Kwok Leung Cheung - Josephine Mun Yee Ko - Yee Peng Phoon - Pui Man Chiu - Paulisally Hau Yi Lo -

Source: https://link.springer.com/







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