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Article: CD71+ population enriched by HPV-E6 protein promotes cancer aggressiveness and radioresistance in cervical cancer cells

TitleCD71+ population enriched by HPV-E6 protein promotes cancer aggressiveness and radioresistance in cervical cancer cells
Authors
Issue Date2019
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/
Citation
Molecular Cancer Research, 2019, v. 17 n. 9, p. 1867-1880 How to Cite?
AbstractA subpopulation of cells within tumors has been suggested to possess the ability to initiate tumorigenesis and contribute to resistance to cancer therapy. Identification and isolation of this subpopulation in cancer cells can be achieved by detecting specific cell-surface markers. In this study, flow cytometry analysis revealed an abundant CD71(+) subpopulation in HPV-positive cervical cancer cells, while limited CD71(+) cells were detected in HPV-negative cervical cancer cells. Furthermore, ectopic expression of the HPV-E6 protein in HPV-negative C33A cells enriched the CD71(+) subpopulation. The CD71(+) subpopulation isolated from the C33A cell line and an HPV-E6-overexpressing clone exhibited enhanced transforming ability, proliferation and resistance to irradiation. In contrast, suppression of CD71 in HPV-positive SiHa cells and the HPV-E6-overexpressing stable clone inhibited spheroid formation and in vitro and in vivo tumorigenicity and sensitized cells to irradiation treatment. CRISPR/Cas9 knockout of CD71 in SiHa cells also produced similar inhibitory effects on tumorigenicity. Double knockout of CD71 and CD55 reversed the oncogenic properties of the HPV-E6-overexpressing clone. These findings suggest that the HPV-E6 protein enriches the subpopulation of CD71(+) cells in cervical cancer, which exhibit cancer stem-like cell properties and are resistant to irradiation treatment. Targeting the CD71(+) subpopulation in cervical cancer cells with siRNAs or CRISPR/Cas9 may provide new insights for the development of novel therapeutic approaches for treating cervical cancer. Implications: We describe the enrichment of CD71(+) population by HPV-E6 protein in cervical cancer cells that promotes cancer aggressiveness and resistance to irradiation treatment.
Persistent Identifierhttp://hdl.handle.net/10722/272378
ISSN
2020 Impact Factor: 5.852
2020 SCImago Journal Rankings: 2.273
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, THY-
dc.contributor.authorTang, HWM-
dc.contributor.authorSiu, MKY-
dc.contributor.authorChan, DW-
dc.contributor.authorChan, KKL-
dc.contributor.authorCheung, ANY-
dc.contributor.authorNgan, HYS-
dc.date.accessioned2019-07-20T10:41:08Z-
dc.date.available2019-07-20T10:41:08Z-
dc.date.issued2019-
dc.identifier.citationMolecular Cancer Research, 2019, v. 17 n. 9, p. 1867-1880-
dc.identifier.issn1541-7786-
dc.identifier.urihttp://hdl.handle.net/10722/272378-
dc.description.abstractA subpopulation of cells within tumors has been suggested to possess the ability to initiate tumorigenesis and contribute to resistance to cancer therapy. Identification and isolation of this subpopulation in cancer cells can be achieved by detecting specific cell-surface markers. In this study, flow cytometry analysis revealed an abundant CD71(+) subpopulation in HPV-positive cervical cancer cells, while limited CD71(+) cells were detected in HPV-negative cervical cancer cells. Furthermore, ectopic expression of the HPV-E6 protein in HPV-negative C33A cells enriched the CD71(+) subpopulation. The CD71(+) subpopulation isolated from the C33A cell line and an HPV-E6-overexpressing clone exhibited enhanced transforming ability, proliferation and resistance to irradiation. In contrast, suppression of CD71 in HPV-positive SiHa cells and the HPV-E6-overexpressing stable clone inhibited spheroid formation and in vitro and in vivo tumorigenicity and sensitized cells to irradiation treatment. CRISPR/Cas9 knockout of CD71 in SiHa cells also produced similar inhibitory effects on tumorigenicity. Double knockout of CD71 and CD55 reversed the oncogenic properties of the HPV-E6-overexpressing clone. These findings suggest that the HPV-E6 protein enriches the subpopulation of CD71(+) cells in cervical cancer, which exhibit cancer stem-like cell properties and are resistant to irradiation treatment. Targeting the CD71(+) subpopulation in cervical cancer cells with siRNAs or CRISPR/Cas9 may provide new insights for the development of novel therapeutic approaches for treating cervical cancer. Implications: We describe the enrichment of CD71(+) population by HPV-E6 protein in cervical cancer cells that promotes cancer aggressiveness and resistance to irradiation treatment.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/-
dc.relation.ispartofMolecular Cancer Research-
dc.titleCD71+ population enriched by HPV-E6 protein promotes cancer aggressiveness and radioresistance in cervical cancer cells-
dc.typeArticle-
dc.identifier.emailSiu, MKY: mkysiu@hku.hk-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.emailChan, KKL: kklchan@hkucc.hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.authoritySiu, MKY=rp00275-
dc.identifier.authorityChan, DW=rp00543-
dc.identifier.authorityChan, KKL=rp00499-
dc.identifier.authorityCheung, ANY=rp00542-
dc.identifier.authorityNgan, HYS=rp00346-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1541-7786.MCR-19-0068-
dc.identifier.pmid31235657-
dc.identifier.scopuseid_2-s2.0-85071783471-
dc.identifier.hkuros298773-
dc.identifier.volume17-
dc.identifier.issue9-
dc.identifier.spage1867-
dc.identifier.epage1880-
dc.identifier.isiWOS:000489645300008-
dc.publisher.placeUnited States-
dc.identifier.issnl1541-7786-

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