scholarly journals PCGF2 and PCGF4 Opposite Drive Stem-like Properties in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jinjing Hu ◽  
Yongqiang Zhou ◽  
Huan Feng ◽  
Yi Xie ◽  
Kuo Qi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
P38 Mapk ◽  
Cell Lines ◽  
Cell Counting ◽  
Stem Cell Population ◽  
Liver Cancer Stem Cells ◽  
Sphere Formation

Abstract Background: PCGF4 is highly expressed in liver cancer and can be used as a marker for liver cancer stem cells. However, PCGF2, a homologue of PCGF4, is not clear whether it is expressed in HCC, and whether it regulates the stemness of liver cancer stem cells.Methods: IHC and Western blot were used to detect the expression of PCGF2 and PCGF4 protein in human HCC tissues and cell lines. Flow cytometry and sphere formation were performed to detect the effect of PCGF2 or PCGF4 on the stem-like properties of liver cancer stem cells. Kaplan-Meier curves were conducted for OS and DFS. Cell viability was measured at the indicated time points using Cell Counting Kit-8. We performed KEGG analysis on these target genes through the cluster profiler package of the R language.Results: IHC results showed that PCGF2 was lower expressed in HCC, while PCGF4 was higher expressed in HCC compared with matched paracancerous, and this higher expression exhibited poor prognosis in HCC. Up regulation of PCGF2 was also accompanied with decreased stem-like properties and sphere formation in HCC cell lines. Interestingly, down regulating PCGF4 got the similar results as up regulating PCGF2. Furthermore, up regulating PCGF2 or down regulating PCGF4 cells performed more sensitivity to sorafenib. We also found that PCGF2 and PCGF4 oppositely regulated the drives stem-like properties by p38 MAPK signal pathway.Conclusion: PCGF2 was a novel negative regulator of LCSCs that inhibiting the stem cell population, reducing the sphere formation ability of liver cancer stem cells, and increasing the sensitivity of sorafenib by targeting p38 MAPK signaling. PCGF2 was supposed to be a novel therapeutic target for Liver cancer stem cell.

scholarly journals Efficacy of Using Cancer Stem Cell Markers in Isolating and Characterizing Liver Cancer Stem Cells

2013 ◽  
Vol 22 (19) ◽  
pp. 2655-2664 ◽  
Author(s):  
George S. Wilson ◽  
Zenan Hu ◽  
Wei Duan ◽  
Aiping Tian ◽  
Xin M. Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Cancer Stem Cell ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Cancer Stem Cell Markers ◽  
Liver Cancer Stem Cells

scholarly journals A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1198 ◽  
Author(s):  
Zeynep Firtina Karagonlar ◽  
Soheil Akbari ◽  
Mustafa Karabicici ◽  
Eren Sahin ◽  
Sanem Tercan Avci ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Cell Line ◽  
Tumor Cells ◽  
Cell Phenotype ◽  
High Plasticity ◽  
Liver Cancer Stem Cells

The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM+/CD133+ liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM−/CD133− non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of β-CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM−/CD133− non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM−/CD133− non-stem cells attained an in vivo tumor forming ability comparable to EpCAM+/CD133+ LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM+/CD133+ LCSCs in HuH7 HCC cells.

scholarly journals Liver Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2800-2805 ◽  
Author(s):  
Stewart Sell ◽  
Hyam L. Leffert
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Liver Cancer Stem Cells ◽  
Liver Stem Cells ◽  
Carcinogenic Process ◽  
Liver Cancer Stem Cell ◽  
New Hypothesis

In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

scholarly journals The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Yan Xiang ◽  
Ting Yang ◽  
Bing-yao Pang ◽  
Ying Zhu ◽  
Yong-ning Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Review Article ◽  
Curative Effect ◽  
The Past ◽  
Liver Cancer Stem Cells

Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with “stem-like” characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a “global” marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies.

scholarly journals The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wang Yin ◽  
Dongxi Xiang ◽  
Tao Wang ◽  
Yumei Zhang ◽  
Cuong V. Pham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
High Performance ◽  
Annexin V ◽  
Intracellular Concentration ◽  
Liver Cancer Stem Cells ◽  
Chemotherapy Agent ◽  
Future Strategy ◽  
Annexin V Assay

AbstractTwo ATP-binding cassette transporters, ABCB1/MDR1 and ABCG2/BCRP, are considered the most critical determinants for chemoresistance in hepatocellular carcinoma. However, their roles in the chemoresistance in liver cancer stem cells remain elusive. Here we explored the role of inhibition of MDR1 or ABCG2 in sensitizing liver cancer stem cells to doxorubicin, the most frequently used chemotherapeutic agent in treating liver cancer. We show that the inhibition of MDR1 or ABCG2 in Huh7 and PLC/PRF/5 cells using either pharmacological inhibitors or RNAi resulted in the elevated level of intracellular concentration of doxorubicin and the accompanied increased apoptosis as determined by confocal microscopy, high-performance liquid chromatography, flow cytometry, and annexin V assay. Notably, the inhibition of MDR1 or ABCG2 led to the reversal of the chemoresistance, as evident from the enhanced death of the chemoresistant liver cancer stem cells in tumorsphere-forming assays. Thus, the elevation of effective intracellular concentration of doxorubicin via the inhibition of MDR1 or ABCG2 represents a promising future strategy that transforms doxorubicin from a traditional chemotherapy agent into a robust killer of liver cancer stem cells for patients undergoing transarterial chemoembolization.

MK2206 overcomes the resistance of human liver cancer stem cells to sorafenib by inhibition of pAkt and upregulation of pERK

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 8047-8055 ◽  
Author(s):  
Beibei Zhai ◽  
Xiaofeng Zhang ◽  
Bin Sun ◽  
Lu Cao ◽  
Linlin Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Human Liver ◽  
Liver Cancer Stem Cells ◽  
Human Liver Cancer

The clinical, prognostic and therapeutic significance of liver cancer stem cells and their markers

2021 ◽  
pp. 101664
Author(s):  
Izabela Zarębska ◽  
Arkadiusz Gzil ◽  
Justyna Durślewicz ◽  
Damian Jaworski ◽  
Paulina Antosik ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Liver Cancer Stem Cells

scholarly journals Inhibition of β‑catenin protein expression by triptolide affects self-renewal of liver cancer stem cells

2015 ◽  
Vol 10 (2) ◽  
pp. 455 ◽  
Author(s):  
Jian-Bo Zhou ◽  
Gang Peng ◽  
Yu-Cheng Jia ◽  
Jun Li ◽  
Jia Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Inhibitory Concentration ◽  
The Self ◽  
Tripterygium Wilfordii ◽  
Self Renewal ◽  
Liver Cancer Stem Cells ◽  
Novel Agent

<p>The present study demonstrates the effects of triptolide, one of the constituents from Tripterygium wilfordii, on the self‑renewal capacity of human hepatocellular carcinoma. The investigation revealed that triptolide markedly prevented the proliferation of liver cancer stem cells (LCSCs). For the LCSCs the minimum inhibitory concentration of triptolide was 0.6 μM. There was a significant and obvious decrease in the capacity of LCSCs to form self-sphere. Furthermore, triptolide reduced the sphere-forming capacity of LCSCs along with inhibition of β‑catenin expression. However, the exposure of triptolide-treated cells to lithium chloride, an activator the Wnt/β-catenin signaling pathway, reversed the triptolide-induced inhibition of β-catenin expression and inhibited the self-renewal capacity. Therefore, triptolide effectively eradicates LCSCs through the inhibition of β-catenin protein and may act as a novel agent for the treatment of hepatocellular carcinoma.</p><p> </p>

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