Aberrantly elevated redox sensing factor Nrf2 promotes cancer stem cell survival via enhanced transcriptional regulation of ABCG2 and Bcl-2/Bmi-1 genes.
The presence of cancer stem cells in cervical cancer stem cells (CSCs) is important in the prevention of therapy failure and tumor recurrence. Upregulation of transcriptional regulation of redox sensing factor Nrf2 leads to the overexpression of drug efflux proteins such as ABCG2 in cancer stem cells and thus results in cancer treatment failure and cancer relapse. In the present study, we purified approximately 3.1% of cervical CSCs, which exhibited aberrant upregulation of Nrf2 in conjunction with an elevated transcriptional regulation of ABCG2, Bcl-2 and Bmi-1. Consequently, CSCs possess prolonged cell survival, infinite cell proliferation and highly resistant apoptosis. Following silencing of the function of Nrf2 the cervical CSCs became more sensitive to DNA targeting drugs and apoptosis. Our results suggested that Nrf2-mediated drug and apoptosis resistance are important in cancer therapies and tumor recurrence. Therefore, designing anticancer drugs targeting Nrf2 may be crucial to prevent CSC-mediated tumorigenesis.
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
Yan
Y
Jia
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
Jun
J
Chen
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
He
H
Zhu
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
Zan-Hui
ZH
Jia
Department of Obstetrics and Gynecology, The Second Hospital of Jilin Universty, Changchun, Jilin 130041, P.R. China.
Man-Hua
MH
Cui
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000502:physiology*; D010084:Oxidation-Reduction; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; C069077:BMI1 protein, human; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D063150:Polycomb Repressive Complex 1