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Article: Octamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathway

TitleOctamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathway
Authors
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2010, v. 52 n. 2, p. 528-539 How to Cite?
AbstractChemoresistance presents a major obstacle to the efficacy of chemotherapeutic treatment of cancers. Using chemotherapeutic drugs to select drug-resistant cancer cells in hepatocellular carcinoma (HCC) and several other cancer cell lines, we demonstrate that chemoresistant cells displayed cancer stem cell features, such as increased self-renewal ability, cell motility, multiple drug resistance, and tumorigenicity. Octamer 4 (Oct4) messenger RNA (mRNA) levels were dramatically increased in chemoresistant cancer cells due to DNA demethylation regulation of Oct4. By functional study, Oct4 overexpression enhanced whereas Oct4 knockdown reduced liver cancer cell resistance to chemotherapeutic drugs in vitro and in xenograft tumors. It is known that the Oct4-TCL1-AKT pathway acts on embryonic stem cells and cancer stem cells in cell proliferation through inhibition of apoptosis. We further demonstrate that Oct4 overexpression induced activation of TCL1, AKT, and ABCG2 to mediate chemoresistance, which can be overcome by addition of the PI3K/AKT inhibitor; therefore, a direct pathway of Oct4-TCL1-AKT-ABCG2 or a combination of Oct4-TCL1-AKT with the AKT-ABCG2 pathway could be a potential new mechanism involved in liver cancer cell chemoresistance. Moreover, the clinical significance of the Oct4-AKT-ABCG2 pathway can be demonstrated in HCC patients, with a strong correlation of expression patterns in human HCC tumors. The role of the Oct4-AKT-ABCG2 axis in cancer cell chemoresistant machinery suggests that AKT pathway inhibition (PI3K inhibitors) not only inhibits cancer cell proliferation, but may also enhance chemosensitivity by target potential chemoresistant cells. Conclusion: Oct4, a transcriptional factor of pluripotent cells, can mediate chemoresistance through a potential Oct4-AKT-ABCG2 pathway. Copyright © 2010 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/129389
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, XQen_HK
dc.contributor.authorOngkeko, WMen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorYang, ZFen_HK
dc.contributor.authorLu, Pen_HK
dc.contributor.authorChen, KKen_HK
dc.contributor.authorLopez, JPen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.date.accessioned2010-12-23T08:36:39Z-
dc.date.available2010-12-23T08:36:39Z-
dc.date.issued2010en_HK
dc.identifier.citationHepatology, 2010, v. 52 n. 2, p. 528-539en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129389-
dc.description.abstractChemoresistance presents a major obstacle to the efficacy of chemotherapeutic treatment of cancers. Using chemotherapeutic drugs to select drug-resistant cancer cells in hepatocellular carcinoma (HCC) and several other cancer cell lines, we demonstrate that chemoresistant cells displayed cancer stem cell features, such as increased self-renewal ability, cell motility, multiple drug resistance, and tumorigenicity. Octamer 4 (Oct4) messenger RNA (mRNA) levels were dramatically increased in chemoresistant cancer cells due to DNA demethylation regulation of Oct4. By functional study, Oct4 overexpression enhanced whereas Oct4 knockdown reduced liver cancer cell resistance to chemotherapeutic drugs in vitro and in xenograft tumors. It is known that the Oct4-TCL1-AKT pathway acts on embryonic stem cells and cancer stem cells in cell proliferation through inhibition of apoptosis. We further demonstrate that Oct4 overexpression induced activation of TCL1, AKT, and ABCG2 to mediate chemoresistance, which can be overcome by addition of the PI3K/AKT inhibitor; therefore, a direct pathway of Oct4-TCL1-AKT-ABCG2 or a combination of Oct4-TCL1-AKT with the AKT-ABCG2 pathway could be a potential new mechanism involved in liver cancer cell chemoresistance. Moreover, the clinical significance of the Oct4-AKT-ABCG2 pathway can be demonstrated in HCC patients, with a strong correlation of expression patterns in human HCC tumors. The role of the Oct4-AKT-ABCG2 axis in cancer cell chemoresistant machinery suggests that AKT pathway inhibition (PI3K inhibitors) not only inhibits cancer cell proliferation, but may also enhance chemosensitivity by target potential chemoresistant cells. Conclusion: Oct4, a transcriptional factor of pluripotent cells, can mediate chemoresistance through a potential Oct4-AKT-ABCG2 pathway. Copyright © 2010 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshATP-Binding Cassette Transporters - physiology-
dc.subject.meshCarcinoma, Hepatocellular - drug therapy-
dc.subject.meshDrug Resistance, Neoplasm - physiology-
dc.subject.meshLiver Neoplasms - drug therapy-
dc.subject.meshOctamer Transcription Factor-3 - physiology-
dc.titleOctamer 4 (Oct4) mediates chemotherapeutic drug resistance in liver cancer cells through a potential Oct4-AKT-ATP-binding cassette G2 pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=52&issue=2&spage=528&epage=539&date=2010&atitle=Octamer+4+(Oct4)+mediates+chemotherapeutic+drug+resistance+in+liver+cancer+cells+through+a+potential+Oct4-AKT-ATP-binding+cassette+G2+pathway-
dc.identifier.emailWang, XQ: xqwang@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityWang, XQ=rp00507en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/hep.23692en_HK
dc.identifier.pmid20683952-
dc.identifier.scopuseid_2-s2.0-77955699082en_HK
dc.identifier.hkuros176610en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955699082&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume52en_HK
dc.identifier.issue2en_HK
dc.identifier.spage528en_HK
dc.identifier.epage539en_HK
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000280513900015-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10003451956-
dc.identifier.scopusauthoridWang, XQ=17343159900en_HK
dc.identifier.scopusauthoridOngkeko, WM=8608904500en_HK
dc.identifier.scopusauthoridChen, L=7409440074en_HK
dc.identifier.scopusauthoridYang, ZF=14018809600en_HK
dc.identifier.scopusauthoridLu, P=55041426400en_HK
dc.identifier.scopusauthoridChen, KK=36485996800en_HK
dc.identifier.scopusauthoridLopez, JP=12800486100en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK

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