scholarly journals Treatment with the herbal formula Songyou Yin inhibits epithelial-mesenchymal transition in hepatocellular carcinoma through downregulation of TGF-β1 expression and inhibition of the SMAD2/3 signaling pathway

2017 ◽  
Vol 13 (4) ◽  
pp. 2309-2315 ◽  
Author(s):  
Susu Zheng ◽  
Qingan Jia ◽  
Hujia Shen ◽  
Xin Xu ◽  
Jiajia Ling ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Herbal Formula ◽  
Mesenchymal Transition ◽  
Tgf Β1

scholarly journals MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Bin Yang ◽  
Chunping Wang ◽  
Hui Xie ◽  
Yiwu Wang ◽  
Jiagan Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Notch Signaling Pathway ◽  
Advanced Hepatocellular Carcinoma ◽  
Targeted Agents ◽  
Mesenchymal Transition ◽  
Molecular Targeted Agents ◽  
Hcc Cells

Abstract Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

scholarly journals Metadherin–PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT–β-catenin signaling pathway

2019 ◽  
Vol 41 (2) ◽  
pp. 130-138 ◽  
Author(s):  
Kai Zhu ◽  
Yuanfei Peng ◽  
Jinwu Hu ◽  
Hao Zhan ◽  
Liuxiao Yang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Arginine Methyltransferase ◽  
Mesenchymal Transition ◽  
Functional Assays ◽  
In Vivo Experiments ◽  
Hcc Cells

Abstract Accumulating data suggest that metadherin (MTDH) may function as an oncogene. Our previous study showed that MTDH promotes hepatocellular carcinoma (HCC) metastasis via the epithelial-mesenchymal transition. In this study, we aim to further elucidate how MTDH promotes HCC metastasis. Using Co-immunoprecipitation (co-IP) and mass spectrometry, we found that MTDH can specifically bind to protein arginine methyltransferase 5 (PRMT5). Further functional assays revealed that PRMT5 overexpression promoted the proliferation and motility of HCC cells and that knockout of PRMT5 impeded the effect of MTDH. The immunohistochemistry assay/tissue microarray results showed that when MTDH was overexpressed in HCC cells, PRMT5 translocated from the nucleus to the cytoplasm, with the subsequent translocation of β-catenin from the cytoplasm to the nucleus and upregulation of the WNT–β-catenin signaling pathway. Further in vivo experiments suggested that PRMT5 and β-catenin played a pivotal role in MTDH-mediated HCC metastasis. We therefore concluded that the MTDH–PRMT5 complex promotes HCC metastasis by regulating the WNT–β-catenin signaling pathway.

scholarly journals PEG10 is imperative for TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma

2016 ◽  
Vol 37 (1) ◽  
pp. 510-518 ◽  
Author(s):  
Minfeng Zhang ◽  
Chengjun Sui ◽  
Binghua Dai ◽  
Weifeng Shen ◽  
Jiongjiong Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Tgf Β1

scholarly journals The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-β/Smad Pathways

2020 ◽  
Vol 10 (4) ◽  
pp. 648-655
Author(s):  
Syarinta Adenina ◽  
Melva Louisa ◽  
Vivian Soetikno ◽  
Wawaimuli Arozal ◽  
Septelia Inawati Wanandi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Hepg2 Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Sorafenib Treatment ◽  
Mesenchymal Transition ◽  
The Impact ◽  
Tgf Β1 ◽  
E Cadherin

Purpose : This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Methods: Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 μM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-β1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-β1, TGF-β1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase–polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Results: Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P<0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P<0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P>0.05). In line with our findings, the expressions of TGF-β1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P<0.05) versus control. Conclusion: Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial–mesenchymal transition markers by activating TGF-β/Smad pathways.

scholarly journals Ursolic Acid Attenuates TGF-β1-Induced Epithelial‐Mesenchymal Transition in NSCLC by Targeting Integrin αVβ5/MMPs Signaling

2019 ◽  
Vol 27 (5) ◽  
pp. 593-600 ◽  
Author(s):  
Jun Shan Ruan ◽  
Huan Zhou ◽  
Lin Yang ◽  
Ling Wang ◽  
Zong Sheng Jiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ursolic Acid ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Nsclc Cell Line ◽  
Mesenchymal Transition ◽  
New Findings ◽  
Underlying Mechanisms ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1)-induced epithelial‐mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1‐integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway-mediated integrin αVβ5 expression, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.

scholarly journals FERMT1 knockdown inhibits oral squamous cell carcinoma cell epithelial-mesenchymal transition by inactivating the PI3K/AKT signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiao Wang ◽  
Qianqian Chen
Keyword(s):  
Oral Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Western Blotting ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background The metastasis of oral cancer is one of the main causes of death. However, the mechanisms underlying oral cancer metastasis have not been completely elucidated. Fermitin family member 1 (FERMT1) plays an -oncogene role in many cancers; however, the role of FERMT1 in oral squamous cell cancer (OSCC) remains unclear. Methods In this study, OSCC cells were treated with 5 ng/ml recombinant human Transforming growth factor-β1 (TGF-β1) protein. FERMT1 expression was measured in OSCC cell lines by RT-qPCR and western blotting. The effect of FERMT1 knockdown on the migration and invasion of OSCC cells was evaluated by Transwell assay. The epithelial-mesenchymal transition (EMT) and PI3K/AKT signaling pathway-related mRNA expression and protein levels were assessed by RT-qPCR and western blotting. Results We found that FERMT1 expression was elevated in TGF-β1-induced OSCC cell lines, and knockdown of FERMT1 inhibited the migration and invasion in TGF-β1-induced OSCC cells. FERMT1 silencing inhibited vimentin, N-cadherin, matrix metalloproteinase 9 (MMP-9) expression and promoted E-cadherin expression, suggesting that FERMT1 silencing inhibited EMT in TGF-β1-induced OSCC cells. Furthermore, FERMT1 silencing inactivated the PI3K/AKT signaling pathway in TGF-β1-induced OSCC cells. Activation of the PI3K/AKT signaling pathway reversed the effect of FERMT1 silencing on OSCC cell migration, invasion, and EMT. Conclusions FERMT1 silencing inhibits the migration, invasion, and EMT of OSCC cells via inactivation of the PI3K/AKT signaling pathway, suggesting that FERMT1 is a novel and potential therapeutic target for anti-metastatic strategies for OSCC.

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