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Article: Therapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin

TitleTherapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin
Authors
Issue Date2015
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2015, v. 5, p. Article no. 9979 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is an EBV-associated epithelial malignancy prevalent in southern China. Presence of treatment-resistant cancer stem cells (CSC) may associate with tumor relapse and metastasis in NPC. ICG-001 is a specific CBP/β-catenin antagonist that can block CBP/β-catenin-mediated transcription of stem cell associated genes and enhance p300/β-catenin-mediated transcription, thereby reducing the CSC-like population via forced differentiation. In this study, we aimed to evaluate the effect of ICG-001 on the CSC-like population, and the combination effect of ICG-001 with cisplatin in the C666-1 EBV-positive NPC cells. Results showed that ICG-001 inhibited C666-1 cell growth and reduced expression of CSC-associated proteins with altered expression of epithelial-mesenchymal transition (EMT) markers. ICG-001 also inhibited C666-1 tumor sphere formation, accompanied with reduced SOX2 hi /CD44 hi CSC-like population. ICG-001 was also found to restore the expression of a tumor suppressive microRNA-145 (miR-145). Ectopic expression of miR-145 effectively repressed SOX2 protein expression and inhibited tumor sphere formation. Combination of ICG-001 with cisplatin synergistically suppressed in vitro growth of C666-1 cells and significantly suppressed growth of NPC xenografts. These results suggested that therapeutically targeting of the CBP/β-catenin signaling pathway with ICG-001 can effectively reduce the CSC-like population and combination with cisplatin can effectively suppress the growth of NPC.
Persistent Identifierhttp://hdl.handle.net/10722/211611
ISSN
2015 Impact Factor: 5.228
2015 SCImago Journal Rankings: 2.073
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, KC-
dc.contributor.authorChan, LS-
dc.contributor.authorIp, JCY-
dc.contributor.authorLo, C-
dc.contributor.authorYip, TTC-
dc.contributor.authorNgan, RKC-
dc.contributor.authorWong, RNS-
dc.contributor.authorLo, KW-
dc.contributor.authorNg, WT-
dc.contributor.authorLee, AWM-
dc.contributor.authorTsao, GSW-
dc.contributor.authorKahn, M-
dc.contributor.authorMak, NK-
dc.contributor.authorLung, ML-
dc.date.accessioned2015-07-21T02:04:42Z-
dc.date.available2015-07-21T02:04:42Z-
dc.date.issued2015-
dc.identifier.citationScientific Reports, 2015, v. 5, p. Article no. 9979-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/211611-
dc.description.abstractNasopharyngeal carcinoma (NPC) is an EBV-associated epithelial malignancy prevalent in southern China. Presence of treatment-resistant cancer stem cells (CSC) may associate with tumor relapse and metastasis in NPC. ICG-001 is a specific CBP/β-catenin antagonist that can block CBP/β-catenin-mediated transcription of stem cell associated genes and enhance p300/β-catenin-mediated transcription, thereby reducing the CSC-like population via forced differentiation. In this study, we aimed to evaluate the effect of ICG-001 on the CSC-like population, and the combination effect of ICG-001 with cisplatin in the C666-1 EBV-positive NPC cells. Results showed that ICG-001 inhibited C666-1 cell growth and reduced expression of CSC-associated proteins with altered expression of epithelial-mesenchymal transition (EMT) markers. ICG-001 also inhibited C666-1 tumor sphere formation, accompanied with reduced SOX2 hi /CD44 hi CSC-like population. ICG-001 was also found to restore the expression of a tumor suppressive microRNA-145 (miR-145). Ectopic expression of miR-145 effectively repressed SOX2 protein expression and inhibited tumor sphere formation. Combination of ICG-001 with cisplatin synergistically suppressed in vitro growth of C666-1 cells and significantly suppressed growth of NPC xenografts. These results suggested that therapeutically targeting of the CBP/β-catenin signaling pathway with ICG-001 can effectively reduce the CSC-like population and combination with cisplatin can effectively suppress the growth of NPC.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.titleTherapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin-
dc.typeArticle-
dc.identifier.emailIp, JCY: josephip@hku.hk-
dc.identifier.emailLee, AWM: awmlee@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityLee, AWM=rp02056-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/srep09979-
dc.identifier.pmcidPMC4404684-
dc.identifier.scopuseid_2-s2.0-84928382257-
dc.identifier.hkuros244743-
dc.identifier.volume5-
dc.identifier.spageArticle no. 9979-
dc.identifier.epageArticle no. 9979-
dc.identifier.isiWOS:000353280700003-
dc.publisher.placeUnited Kingdom-

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