Invasion and EMT-associated genes are up-regulated in B viral hepatocellular carcinoma with high expression of CD133-human and cell culture study

Na, Deuk Chae; Lee, Jae Eun; Yoo, Jeong Eun; Oh, Bong-Kyeong; Choi, Gi Hong; Park, Young Nyun

doi:10.1016/j.yexmp.2010.10.003

Cited by 41 publications

(38 citation statements)

References 35 publications

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“…Differences between the in vitro and in vivo situation were identified, which may be induced by the effect of extracellular matrix interactions in the xenograft model (21) since matrix stiffness influences proliferation and chemotherapeutic resistance as well as cellular dormancy and stem cell characteristics in HCC (31). Notably, CD133 expression was only observed in Hep3B cells, which confirms the results of a recent study revealing that CD133 expression levels are associated with the upregulation of invasion-and EMT-associated genes leading to greater cell migration in various human hepatic cancer cell lines (32). This reflects the whole differentiation capacity of human liver cancer (17,18), which should be the concept for further experimental investigations and the new future approach for patient risk stratification and therapeutic decision, as it has assumed strong relevance in other solid malignancies including breast cancer (33,34).…”

Section: Discussionsupporting

confidence: 83%

The pan-deacetylase inhibitor panobinostat modulates the expression of epithelial-mesenchymal transition markers in hepatocellular carcinoma models

et al. 2012

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Abstract. Deacetylase inhibitors (DACis) represent a novel therapeutic option for human cancers by classically affecting proliferation or apoptosis. Since transdifferentiation and dedifferentiation play a key role in carcinogenesis, we investigated the epigenetic influence on the molecular differentiation status in human hepatocellular carcinoma (HCC) models. Markers of differentiation, including cytokeratin (Ck) 7, Ck8, Ck18, Ck19, Ck20, vimentin, sonic hedgehog homolog (SHH), smoothened (Smo), patched (Ptc), glioma-associated oncogene homolog 1 (Gli1), CD133, octamer-binding transcription factor 4 (Oct4) and β-catenin, were examined in the human HCC cell lines HepG2 and Hep3B in vitro and in vivo (xenograft model) using quantitative real-time PCR and immunohistochemistry following treatment with the pan-DACi panobinostat (LBH589). Compared to untreated controls, treated HepG2 xenografts, and to a lesser extent cell lines, demonstrated a significant increase of differentiation markers Ck7 and Ck19 (classical cholangiocellular type) and Ck8 and Ck18 (classical HCC type), and a decreased level of dedifferentiation markers vimentin (mesenchymal) and SHH/Ptc (embryonic), paralleled with a more membranous expression of β-catenin. These findings were dose-dependently correlated with tumor size, necrosis rate, microvessel density and mitosis/Ki-67-associated proliferation rate. Our results demonstrate that the differentiation status of human HCC cells is influenced by the pan-DACi panobinostat, indicating that this treatment may influence the epithelial-mesenchymal transition (EMT) status related to metastasis and aggressiveness.

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Section: Discussionsupporting

confidence: 83%

The pan-deacetylase inhibitor panobinostat modulates the expression of epithelial-mesenchymal transition markers in hepatocellular carcinoma models

et al. 2012

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“…CSCs in HCC expressed higher level of EMT regulators, such as Twist and Snail (Na et al, 2011). Upregulation of Twist1 in HCC significantly enhanced cell motility, invasiveness and VM formation in 3D culture system as well as expression of VM-associated molecules such as VE-cadherin (Sun et al, 2010).…”

Section: It Is Believed That Epithelial-mesenchymal Transition (Emt) mentioning

confidence: 98%

Contribution of cancer stem cells to tumor vasculogenic mimicry

2011

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Vasculogenic mimicry (VM), a newly-defined pattern of tumor blood supply, provides a special passage without endothelial cells and is conspicuously different from angiogenesis and vasculogenesis. The biological features of the tumor cells that form VM remain unknown. Cancer stem cells (CSCs) are believed to be tumor-initiating cells, capable of self-renewal and multipotent differentiation, which resemble normal stem cells in phenotype and function. Recently CSCs have been shown to contribute to VM formation as well as angiogenesis. These findings challenge the previous understanding of the cellular basis of VM formation. In this review, we present evidence for participation of CSCs in VM formation. We also discuss the potential mechanisms and possible interaction of CSCs with various elements in tumor microenvironment niche. Based on the importance of VM in tumor progression, it constitutes a novel therapeutic target for cancer.

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“…Ren et al [53] demonstrated that the overexpression of Twist in HCC cell line SMMC-7721 can promote the generation of a hepatocellular cancer stem cell (HSC) phenotype through upregulation of the expression of the biomarkers C1D33 and CD44. Na et al [54] reported that upregulation of Twist in HCC cell lines with high expression of C1D33 can generate CSCs which have been reported to have more aggressive biological behavior and more invasive characteristics. Meng et al [55] reported that Twist-regulated miRNAs (such as in miR-181, a mediator of the oncogenic effects of Twist on cancer stem cell invasion in human HCC) may play a part in tumor spreading by modulating the expression of gene products involved in phenotypic characteristics of HSCs such as cell migration, invasion, and chemoresistance [55].…”

Section: Role Of Twist In Hcc Stem Cell Generationmentioning

confidence: 99%

“…CD133 ? sphere-forming cells (SFCs) sorted from the SMMC-7721 cell line, namely hepatic CSC, showed upregulated expression of Twist and downregulated expression of E-cadherin [45,54]. He et al [45] demonstrated that casticin, a flavonol, has potential to target CD133 ?…”

Section: Targeting Twist In Hcc Therapeutics: Success and Promisementioning

confidence: 99%

Twist in hepatocellular carcinoma: pathophysiology and therapeutics

2015

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related disease worldwide. Although HCC is mainly associated with viral hepatitis and alcoholic cirrhosis, numerous physiological and biochemical events are associated with HCC progression. The transcription factor Twist, which plays a key role in epithelial to mesenchymal transition, is reported to be associated with HCC. Overexpression of Twist causes various biochemical changes, such as increase of cell proliferation, reduction of apoptosis, cell cycle deregulation, generation of hepatic cancer stem cells, and in some cases, drug resistance. These changes result in various physiological changes, such as angiogenesis, cellular migration and invasion, and vasculogenic mimicry, which ultimately causes hepatocellular metastasis. Interestingly, targeting Twist via different strategies, especially small RNA technology, has shown promising therapeutic potential for future HCC treatment.

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Invasion and EMT-associated genes are up-regulated in B viral hepatocellular carcinoma with high expression of CD133-human and cell culture study

Cited by 41 publications

References 35 publications

The pan-deacetylase inhibitor panobinostat modulates the expression of epithelial-mesenchymal transition markers in hepatocellular carcinoma models

The pan-deacetylase inhibitor panobinostat modulates the expression of epithelial-mesenchymal transition markers in hepatocellular carcinoma models

Contribution of cancer stem cells to tumor vasculogenic mimicry

Twist in hepatocellular carcinoma: pathophysiology and therapeutics

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