scholarly journals CD24+ Liver Tumor-Initiating Cells Drive Self-Renewal and Tumor Initiation through STAT3-Mediated NANOG Regulation

2011 ◽  
Vol 9 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Terence Kin Wah Lee ◽  
Antonia Castilho ◽  
Vincent Chi Ho Cheung ◽  
Kwan Ho Tang ◽  
Stephanie Ma ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Tumor Initiation ◽  
Tumor Initiating Cells ◽  
Self Renewal

Abstract 2445: CD24+liver tumor-initiating cells drives self-renewal and tumor initiation through Stat3-mediated Nanog regulation

2011 ◽  
Author(s):  
Kin Wah Lee ◽  
Antonia Castilho ◽  
Vincent Chi-Ho Cheung ◽  
Kwan Ho Tang ◽  
Stephanie Ma ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Tumor Initiation ◽  
Tumor Initiating Cells ◽  
Self Renewal

scholarly journals miR-96 Regulates Liver Tumor-Initiating Cells Expansion and Sorafenib Resistance

2020 ◽  
Author(s):  
Yonggang Huang ◽  
Jin Zhang ◽  
Wei Dong ◽  
Huiping Peng ◽  
Maolin Gu ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Underlying Mechanism ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
Functional Studies ◽  
Optimal Target ◽  
The Impact

Abstract Background Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. Methods Real-time PCR was used to detect the expression of miR-96 in liver tumor-initiating cells (T-ICs). The impact of miR-96 on liver T-ICs expansion was investigated both in vivo and in vitro . The correlation between miR-96 expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results Our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates SOX6 via its mRNA 3’UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-96 may predict sorafenib benefits in HCC patients. Conclusion Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC.

scholarly journals The long noncoding RNA lncZic2 drives the self-renewal of liver tumor–initiating cells via the protein kinase C substrates MARCKS and MARCKSL1

2018 ◽  
Vol 293 (21) ◽  
pp. 7982-7992 ◽  
Author(s):  
Zhenzhen Chen ◽  
Yating Liu ◽  
Lintong Yao ◽  
Shiying Guo ◽  
Yanfeng Gao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Liver Cancer ◽  
Liver Tumor ◽  
Noncoding Rna ◽  
The Self ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Kinase C

Liver tumor–initiating cells (TICs) form small subsets of cells in hepatocellular tumors and account for tumorigenesis, metastasis, recurrence, and drug resistance. Recently, we found that the transcription factor Zic family member 2 (ZIC2) is highly expressed in liver TICs and required for their self-renewal. However, the molecular mechanisms underlying self-renewal of liver TICs remain unclear. Here, using expression profiling and CRISPR-interference assays with clinical samples of human liver cancers, we identified a long noncoding RNA (lncRNA), lncZic2, that is located near the ZIC2 locus and was highly expressed in liver cancer and liver TICs. We found that lncZic2 is required for the self-renewal of liver TICs in a ZIC2-independent manner. lncZic2 drove the expression of myristoylated alanine-rich protein kinase C substrate (MARCKS) and MARCKS-like 1 (MARCKSL1), whose expression levels were increased during liver tumorigenesis and liver TIC self-renewal. Mechanistically, lncZic2 interacted with BRM/SWI2-related gene 1 (BRG1) and recruited this transcriptional regulator to the promoters of the MARCKS and MARCKSL1 gene, which activated expression of these genes. Moreover, we noted that depletion of lncZic2 and BRG1 decreases MARCKS and MARCKSL1 expression and diminishes liver TIC levels. In conclusion, lncZic2 is required for the self-renewal of liver TICs by up-regulating MARCKS and MARCKSL1 gene expression via the transcription factor BRG1. Our findings suggest that the lncZic2–BRG1–MARCKS/MARCKSL1 signaling cascade might be a potential target for eliminating liver TICs in the management of liver cancer.

scholarly journals MicroRNA-31 suppresses the self-renewal capability of α2δ1+ liver tumor-initiating cells by targeting ISL1

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87647-87657 ◽  
Author(s):  
Yuan Zhang ◽  
Wei Zhao ◽  
Haibo Han ◽  
Sheng Li ◽  
Dongji Chen ◽  
...  
Keyword(s):  
Liver Tumor ◽  
The Self ◽  
Tumor Initiating Cells ◽  
Self Renewal

miR-361-3p Regulates Liver Tumor-initiating Cells Expansion and Chemo-resistance

2020 ◽  
Author(s):  
Shuping Qu ◽  
Xiaobing Zhang ◽  
Hengwei Fan ◽  
Yue Wu ◽  
Jian Zhai ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Cohort Analysis ◽  
The Self ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Abstract Background: Increasing evidence shows that liver tumor-initiating cells (T-ICs) closely associated with the progression, metastasis, recurrence and chemo-resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. The purpose of our study was to explore the role of miR-361-3p in the expansion of liver T-ICs and the potential molecular mechanism.Results: Flow cytometry analysis was performed to isolate CD24+, CD133+ or EpCAM+ cells from primary HCC cells or HCC cell lines. Real-time PCR was used to detect the expression of miR-361-3p in liver T-ICs. The impact of miR-361-3p on liver T-ICS expansion was investigated both in vivo and in vitro. The correlation between miR-361-3p expression and TACE (transcatheter arterial chemoembolization) or sorafenib benefits in HCC was evaluated in patient cohorts. miR-361-3p expression is upregulated in liver T-ICs. Knockdown of miR-361-3p impairs the self-renewal and tumorigenicity liver T-ICs. Conversely, forced miR-361-3p expression enhances the self-renewal and tumorigenicity liver T-ICs. Mechanistically, miR-361-3p directly targets SOX1 via binding its 3’-UTR in liver T-ICs. Moreover, miR-361-3p knockdown hepatoma cells are more sensitive to cisplatin or sorafenib treatment. Clinical cohort analysis demonstrates that miR-361-3p low HCC patients are benefited from TACE or sorafenib treatment. Conclusions: Our findings revealed the crucial role of the miR-361-3p in liver T-IC expansion and TACE or sorafenib response, rendering miR-361-3p an optimal target for the prevention and intervention in HCC.

CXCL11 promotes self-renewal and tumorigenicity of α2δ1+ liver tumor-initiating cells through CXCR3/ERK1/2 signaling

2019 ◽  
Vol 449 ◽  
pp. 163-171 ◽  
Author(s):  
Yuan Zhang ◽  
Wei Zhao ◽  
Sheng Li ◽  
Mengzhu Lv ◽  
Xiaodan Yang ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Tumor Initiating Cells ◽  
Self Renewal

scholarly journals CD133+ liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin/interleukin-8/CXCL1 signaling

Hepatology ◽  
2012 ◽  
Vol 55 (3) ◽  
pp. 807-820 ◽  
Author(s):  
Kwan Ho Tang ◽  
Stephanie Ma ◽  
Terence K. Lee ◽  
Yuen Piu Chan ◽  
Pak Shing Kwan ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Tumor Angiogenesis ◽  
Interleukin 8 ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Promote Tumor Angiogenesis
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