ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

Zhu, Pingping; Wang, Yanying; He, Lei; Huang, Guanling; Du, Ying; Zhang, Geng; Yan, Xinlong; Xia, Pengyan; Ye, Buqing; Wang, Shuo; Hao, Lu; Wu, Jiayi; Fan, Zusen

doi:10.1172/jci81979

Cited by 134 publications

(134 citation statements)

References 56 publications

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“…CSCs evade the anti-cancer effects of standard chemotherapy on a tumor and have emerged as an underestimated biological barrier to the success of systemic chemotherapy 2,3 . Small groups of CSCs in tumor tissue play an important role in tumor drug resistance 4,5 . Although chemotherapy drugs and chemotherapy regimens are being continuously improved, tumor chemotherapy still aims to reduce the number of cancer cells and shrink the tumor [6][7][8] .…”

Section: Introductionmentioning

confidence: 99%

Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

et al. 2016

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Cancer stem cells (CSCs) are responsible for cancer drug resistance with high expression of ABCG2, which pumps the internalized chemotherapeutic out to escape drug-induced cytotoxicity. Here, we established a functionalized mesoporous silica nanoparticle (MSN) system to deliver shABCG2 and doxorubicin (Dox) synergistically. With excellent cell uptake and endosomal escape capacities, the dual-delivery carriers internalized shABCG2 and Dox into CSCs efficiently. ABCG2 depletion increased intracellular and intranuclear Dox enrichment, drove vigorous Dox-induced cell death, and impaired the self-renewal of CSCs. Additionally, the nanoparticles eliminated tumors efficiently and reduced tumor initiation by CSCs in vivo, with negligible side effects. Our findings suggest that well-designed delivery systems for conventional chemotherapeutic agents are promising for CSC therapy.

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Section: Introductionmentioning

confidence: 99%

Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

et al. 2016

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“…3i). To further verify this result, we used lncBRM -silenced sphere lysates to conduct size fractionation assays as previously described25. BRG1 and BRM constitute the BRG1- and BRM-embedded BAF complex, respectively, which can be detected by sucrose density gradient centrifugation.…”

Section: Resultsmentioning

confidence: 99%

“…6) have been widely used as liver CSC markers, respectively. We recently sorted a small subpopulation from HCC cell lines and HCC samples with these two combined makers and defined this subset of CD13 + CD133 + cells as liver CSCs1125. We performed transcriptome microarray analysis of CD13 + CD133 + (liver CSCs) and CD13 − CD133 − (non-CSCs) cells and identified 286 differentially expressed lncRNAs in liver CSCs compared with that in non-CSCs11.…”

Section: Resultsmentioning

confidence: 99%

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LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells

et al. 2016

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Liver cancer stem cells (CSCs) may contribute to the high rate of recurrence and heterogeneity of hepatocellular carcinoma (HCC). However, the biology of hepatic CSCs remains largely undefined. Through analysis of transcriptome microarray data, we identify a long noncoding RNA (lncRNA) called lncBRM, which is highly expressed in liver CSCs and HCC tumours. LncBRM is required for the self-renewal maintenance of liver CSCs and tumour initiation. In liver CSCs, lncBRM associates with BRM to initiate the BRG1/BRM switch and the BRG1-embedded BAF complex triggers activation of YAP1 signalling. Moreover, expression levels of lncBRM together with YAP1 signalling targets are positively correlated with tumour severity of HCC patients. Therefore, lncBRM and YAP1 signalling may serve as biomarkers for diagnosis and potential drug targets for HCC.

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“…41 Elevated expression of KLF-4 in HCC is significantly correlated with poor tumor differentiation, vascular invasion, overall survival, and recurrence-free survival. 22 As a major pluripotent factor, Oct-4 is highly expressed in liver CSCs [42][43][44] and may contribute to the reprogramming of CSCs. Gli-1 is the main transcription factor in hedgehog signaling pathway, which is activated in various chronic liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

Liu

et al. 2017

Laboratory Investigation

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ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem cells

Cited by 134 publications

References 56 publications

Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles

LncBRM initiates YAP1 signalling activation to drive self-renewal of liver cancer stem cells

Activation of pluripotent genes in hepatic progenitor cells in the transition of nonalcoholic steatohepatitis to pre-malignant lesions

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