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Article: The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma

TitleThe ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma
Authors
KeywordsHCC
Multidrug resistance
Plasticity
Drug transporter
Cancer stemness
Issue Date2019
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2019, v. 457, p. 98-109 How to Cite?
AbstractATP-binding cassette (ABC) transporters mediate multidrug resistance and cancer stem cell properties in various model systems. Yet, their biological significance in cancers, especially in hepatocellular carcinoma (HCC), remains unclear. In this study, we investigated the function of ABCF1 in HCC and explored its potential as a therapeutic target. ABCF1 was highly expressed in fetal mouse livers but not in normal adult livers. ABCF1 expression was upregulated in HCCs. These results demonstrate that ABCF1 functions as a hepatic oncofetal protein. We further demonstrated elevated ABCF1 expression in HCC cells upon acquiring chemoresistance. Suppression of ABCF1 by siRNA sensitized both parental cells and chemoresistant cells to chemotherapeutic agents. Reversely, ABCF1 overexpression promoted chemoresistance and drug efflux. In addition, overexpression of ABCF1 enhanced migration, spheroid and colony formation and epithelial-mesenchymal transition (EMT) induction. RNA sequencing analysis revealed EMT inducers HIF1α/IL8 and Sox4 as potential mediators for the oncogenic effect of ABCF1 in HCC progression. Together, this study illustrates that ABCF1 is a novel potential therapeutic target for HCC treatment.
Persistent Identifierhttp://hdl.handle.net/10722/293215
ISSN
2020 Impact Factor: 8.679
2020 SCImago Journal Rankings: 2.470
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFung, SW-
dc.contributor.authorCheung, PFY-
dc.contributor.authorYip, CW-
dc.contributor.authorNg, LWC-
dc.contributor.authorCheung, TT-
dc.contributor.authorChong, CCN-
dc.contributor.authorLee, C-
dc.contributor.authorLai, PBS-
dc.contributor.authorChan, AWH-
dc.contributor.authorTsao, GSW-
dc.contributor.authorWong, CH-
dc.contributor.authorChan, SL-
dc.contributor.authorLo, KW-
dc.contributor.authorCheung, ST-
dc.date.accessioned2020-11-23T08:13:30Z-
dc.date.available2020-11-23T08:13:30Z-
dc.date.issued2019-
dc.identifier.citationCancer Letters, 2019, v. 457, p. 98-109-
dc.identifier.issn0304-3835-
dc.identifier.urihttp://hdl.handle.net/10722/293215-
dc.description.abstractATP-binding cassette (ABC) transporters mediate multidrug resistance and cancer stem cell properties in various model systems. Yet, their biological significance in cancers, especially in hepatocellular carcinoma (HCC), remains unclear. In this study, we investigated the function of ABCF1 in HCC and explored its potential as a therapeutic target. ABCF1 was highly expressed in fetal mouse livers but not in normal adult livers. ABCF1 expression was upregulated in HCCs. These results demonstrate that ABCF1 functions as a hepatic oncofetal protein. We further demonstrated elevated ABCF1 expression in HCC cells upon acquiring chemoresistance. Suppression of ABCF1 by siRNA sensitized both parental cells and chemoresistant cells to chemotherapeutic agents. Reversely, ABCF1 overexpression promoted chemoresistance and drug efflux. In addition, overexpression of ABCF1 enhanced migration, spheroid and colony formation and epithelial-mesenchymal transition (EMT) induction. RNA sequencing analysis revealed EMT inducers HIF1α/IL8 and Sox4 as potential mediators for the oncogenic effect of ABCF1 in HCC progression. Together, this study illustrates that ABCF1 is a novel potential therapeutic target for HCC treatment.-
dc.languageeng-
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet-
dc.relation.ispartofCancer Letters-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectHCC-
dc.subjectMultidrug resistance-
dc.subjectPlasticity-
dc.subjectDrug transporter-
dc.subjectCancer stemness-
dc.titleThe ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, EMT and cancer stemness in hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailCheung, TT: cheung68@hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.authorityCheung, TT=rp02129-
dc.identifier.authorityTsao, GSW=rp00399-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.canlet.2019.05.010-
dc.identifier.pmid31100412-
dc.identifier.scopuseid_2-s2.0-85065720608-
dc.identifier.hkuros319401-
dc.identifier.volume457-
dc.identifier.spage98-
dc.identifier.epage109-
dc.identifier.isiWOS:000473839400010-
dc.publisher.placeIreland-
dc.identifier.issnl0304-3835-

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