High expression of Snail and NF-κB predicts poor survival in Chinese hepatocellular carcinoma patients

Zhang, Min; Dong, Xin Qi; Zhang, Dengcai; Chen, Xiaojie; Zhu, Xinyu

doi:10.18632/oncotarget.13891

Cited by 14 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The zinc-finger transcriptional repressor Snail reportedly contributes to EMT in HCC and plays a key role in tumorigenesis, differentiation, migration and invasiveness ( 31 ). In addition, recent research has revealed that Snail expression is negatively related to tumor differentiation, which is an independent factor predictive of survival in HCC patients ( 32 ). Loss of E-cadherin and gain of vimentin are known to play key roles in the EMT process of various human types of cancer, including HCC ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition inï¿½vitro through activation of the Hedgehog pathway

et al. 2017

View full text Add to dashboard Cite

Chemokine (C-C motif) ligand 2 (CCL2) has been shown to play an important role in the regulation of tumor cell growth, metastasis and host immune response. CCL2 preferentially binds to the C-C chemokine receptor type 2 (CCR2), which is expressed in various tissues. However, the role of the CCL2/CCR2 axis in hepatocellular carcinoma (HCC) invasion and its molecular mechanisms remain unclear. The aim of this study was to elucidate this issue. The human HCC cell line MHCC-97H was treated with CCL2. Cyclopamine, a smoothened (SMO) antagonist, was used to inhibit SMO activity. CCR2 siRNA and Gli-1 siRNA were used to inhibit CCR2 and Gli-1 expression respectively. The effect of CCL2 and Hedgehog (Hh) signaling on cancer cell epithelial-mesenchymal transition (EMT) and invasion was evaluated by quantitative real-time PCR analysis, western blotting and Transwell invasion assay. Our results revealed that CCL2 induced HCC cell invasion and EMT. This effect was accompanied by the activation of Hh signaling, the upregulation of Snail and vimentin and the reduction of E-cadherin. Notably, prior silencing of CCR2 with siRNA abolished CCL2-induced Hh signaling activation, Snail and vimentin upregulation, E-cadherin reduction, as well as HCC cell invasion and EMT. Furthermore, pretreatment with cyclopamine or predepletion of Gli-1 by siRNA also eliminated the changes of Snail, vimentin and E-cadherin, and HCC invasion and EMT caused by CCL2. Collectively, our results revealed that the link between the CCL2/CCR2 axis and the Hh pathway plays an important role in HCC progression. Therefore, the CCL2/CCR2 axis may represent a promising therapeutic target to prevent HCC progression.

show abstract

Section: Discussionmentioning

confidence: 99%

CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition inï¿½vitro through activation of the Hedgehog pathway

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, there is considerable controversy regarding the role of NF-κB in the development of HCC, as several studies also reported induction of pro-tumorigenic features upon NF-κB inactivation [15,47,55,56]. Nonetheless, it is indisputable that NF-κB can play a direct or indirect role in hepatocarcinogenesis, and that dysregulation can considerably influence clinical outcome [14,57,58].…”

Section: Nf-κb In Hepatocarcinogenesismentioning

confidence: 99%

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Czauderna

Castven

Mahn

et al. 2019

Cancers

View full text Add to dashboard Cite

Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions.

show abstract

“…Snail recruits the histone demethylase lysine-specific demethylase 1 (LSD1), which removes the dimethylation of K4 on histone H3 (H2K4m2) and mediates the transcriptional repression of CDH1 [126]. Elevated Snail levels predict the poor survival of HCC patients [127].…”

Section: Clinical Application Of Epigenetic Alterations As Hepaticmentioning

confidence: 99%

The Epigenetic Regulation of HCC Metastasis

Han

Ban

Hur

et al. 2018

IJMS

View full text Add to dashboard Cite

Epigenetic alterations, such as histone modification, DNA methylation, and miRNA-mediated processes, are critically associated with various mechanisms of proliferation and metastasis in several types of cancer. To overcome the side effects and limited effectiveness of drugs for cancer treatment, there is a continuous need for the identification of more effective drug targets and the execution of mechanism of action (MOA) studies. Recently, epigenetic modifiers have been recognized as important therapeutic targets for hepatocellular carcinoma (HCC) based on their reported abilities to suppress HCC metastasis and proliferation in both in vivo and in vitro studies. Therefore, here, we introduce epigenetic modifiers and alterations related to HCC metastasis and proliferation, and their molecular mechanisms in HCC metastasis. The existing data suggest that the study of epigenetic modifiers is important for the development of specific inhibitors and diagnostic targets for HCC treatment.

show abstract

High expression of Snail and NF-κB predicts poor survival in Chinese hepatocellular carcinoma patients

Cited by 14 publications

References 24 publications

CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition inï¿½vitro through activation of the Hedgehog pathway

CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition inï¿½vitro through activation of the Hedgehog pathway

Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

The Epigenetic Regulation of HCC Metastasis

Contact Info

Product

Resources

About