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Article: Physiological beta-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinoma

TitlePhysiological beta-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinoma
Authors
Issue Date2013
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccellbiol/
Citation
BMC Cell Biology, 2013, v. 14, p. 1-13 How to Cite?
AbstractBACKGROUND: A 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/beta-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological beta-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of beta-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. RESULTS: Introduction of increased beta-catenin signaling, haploid expression of beta-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt/beta-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous beta-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/beta-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-beta, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using beta-catenin shRNA inhibitory assays, a dominant role for beta-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. CONCLUSIONS: Wnt/beta-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/beta-catenin signaling with stemness transition networks.
Persistent Identifierhttp://hdl.handle.net/10722/193173
ISSN
2015 Impact Factor: 2.584
2015 SCImago Journal Rankings: 1.486
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheng, Yen_US
dc.contributor.authorCheung, AKLen_US
dc.contributor.authorKo, JMYen_US
dc.contributor.authorPhoon, YPen_US
dc.contributor.authorChiu, PMen_US
dc.contributor.authorLo, PHen_US
dc.contributor.authorWaterman, MLen_US
dc.contributor.authorLung, MLen_US
dc.date.accessioned2013-12-20T02:28:29Z-
dc.date.available2013-12-20T02:28:29Z-
dc.date.issued2013en_US
dc.identifier.citationBMC Cell Biology, 2013, v. 14, p. 1-13en_US
dc.identifier.issn1471-2121en_US
dc.identifier.urihttp://hdl.handle.net/10722/193173-
dc.description.abstractBACKGROUND: A 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/beta-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological beta-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of beta-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. RESULTS: Introduction of increased beta-catenin signaling, haploid expression of beta-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt/beta-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous beta-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/beta-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-beta, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using beta-catenin shRNA inhibitory assays, a dominant role for beta-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. CONCLUSIONS: Wnt/beta-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/beta-catenin signaling with stemness transition networks.-
dc.languageengen_US
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.biomedcentral.com/bmccellbiol/-
dc.relation.ispartofBMC Cell Biologyen_US
dc.rightsBMC Cell Biology. Copyright © BioMed Central Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlePhysiological beta-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinomaen_US
dc.typeArticleen_US
dc.identifier.emailCheng, Y: yuecheng@hku.hken_US
dc.identifier.emailCheung, AKL: arthurhk@hku.hken_US
dc.identifier.emailKo, JMY: joko@hku.hken_US
dc.identifier.emailChiu, PM: h9994065@hkusua.hku.hken_US
dc.identifier.emailLung, ML: mlilung@hku.hken_US
dc.identifier.authorityCheng, Y=rp01320en_US
dc.identifier.authorityCheung, AKL=rp01769en_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1471-2121-14-44en_US
dc.identifier.pmid24073846-
dc.identifier.pmcidPMC3819748-
dc.identifier.scopuseid_2-s2.0-84884623144-
dc.identifier.hkuros227058en_US
dc.identifier.volume14en_US
dc.identifier.spage1en_US
dc.identifier.epage13en_US
dc.identifier.isiWOS:000326168400001-
dc.publisher.placeUnited Kingdom-

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