14‐3‐3ε Induces Epithelial‐Mesenchymal Transition and Suppresses E‐cadherin Expression via Inducing Zeb‐1 in Hepatocellular Carcinoma

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.

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Downregulation of UBAP2L Inhibits the Epithelial-Mesenchymal Transition via SNAIL1 Regulation in Hepatocellular Carcinoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000470824 ◽

2017 ◽

Vol 41 (4) ◽

pp. 1584-1595 ◽

Cited By ~ 6

Author(s):

Tao Ye ◽

Jing Xu ◽

Ling Du ◽

Wenhui Mo ◽

Yiming Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Cell Lines ◽

Epithelial Mesenchymal Transition ◽

Critical Role ◽

Migration And Invasion ◽

Biological Traits ◽

Mesenchymal Transition ◽

Qrt Pcr ◽

E Cadherin

Background/Aims: Dysregulation of ubiquitin-associated protein 2-like (UBAP2L) has been reported in tumors, but its role in hepatocellular carcinoma (HCC) progression is unclear. Methods: The expression levels of UBAP2L in HCC tissues and HCC cell lines were detected by western blot and quantitative real-time (qRT) PCR. The effects of UBAP2L expression on HCC cell biological traits, including migration and invasion, were investigated by wound healing assay and matrigel transwell assay. Simultaneously, the expression of epithelial-mesenchymal transition (EMT) markers including E-cadherin, CK-18, N-cadherin, Vimentin, Claudin7 and the promoter activity of E-cadherin were detected by western blot and qRT-PCR. Subsequently, role of SNAIL1 in UBAP2L-mediated EMT and the mechanism underlying UBAP2L-mediated SNAIL1 expression were further investigated. Results: UBAP2L was overexpressed in human HCC tissues compared with peri-tumoral tissues. Downregulation of UBAP2L inhibited migration, invasion and the EMT in highly metastatic HCC cell lines. Furthermore, UBAP2L knockdown inhibited expression of the transcriptional repressor SNAIL1 and its ability to bind to the E-cadherin promoter via SMAD2 signaling pathway, which in turn resulted in increased E-cadherin expression. Additionally, bioinformatics analysis showed that expression of UBAP2L is correlated with poor prognosis in patients with HCC. Conclusions: UBAP2L plays a critical role in maintenance of the metastatic ability of HCC cells via SNAIL1 Regulation and is predictive of a poor clinical outcome.

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PHF8 upregulation contributes to autophagic degradation of E-cadherin, epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-018-0890-4 ◽

2018 ◽

Vol 37 (1) ◽

Cited By ~ 10

Author(s):

Wuhua Zhou ◽

Li Gong ◽

Qinchuan Wu ◽

Chunyang Xing ◽

Bajin Wei ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Autophagic Degradation ◽

E Cadherin

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Correction to: PHF8 upregulation contributes to autophagic degradation of E-cadherin, epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1452-0 ◽

2019 ◽

Vol 38 (1) ◽

Author(s):

Wuhua Zhou ◽

Li Gong ◽

Qinchuan Wu ◽

Chunyang Xing ◽

Bajin Wei ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Autophagic Degradation ◽

E Cadherin

In the publication of our publication [1], we have noticed there is a wrong label in Fig. 1e, in which the position of “HCC” and “Adjacent” should be transposed.

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The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5629304 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Shufang Liang ◽

Yong Zou ◽

Jingdong Gao ◽

Xiaolin Liu ◽

Wanfu Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Chinese Herb ◽

Migration And Invasion ◽

Transwell Assay ◽

Mesenchymal Transition ◽

Huh7 Cells ◽

Effective Therapeutic Strategy ◽

E Cadherin

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In China, traditional Chinese herb medicine has been widely used in the treatment of HCC. Jiedu Recipe (JR) is a common used prescription which has shown good results against HCC. However, the exact mechanisms of JR are still unknown. Therefore, we investigated the efficacy of JR on HCC in the current study. JR inhibited the cell viability of both SMMC-7721 and Huh7 cells in both time- and dose-dependent manners. Transwell assay revealed that JR decreased the number of migrated cells of SMMC-7721 cells. JR treatment increased the E-cadherin expression level and decreased the levels of p-Smad2/3 and Smad2/3. Further study showed that JR reversed the effect of TGFβ1 on the expression of E-cadherin, vimentin, N-cadherin, and MMP2/9. JR also significantly inhibited TGFβ1-induced migration and invasion of SMMC-7721 and Huh7 cells determined by wound healing assay and transwell assay. TGFβ1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGFβ1-induced activation of Smad2/3 and Akt and MAPKs. In conclusion, JR inhibits liver cancer cells migration and invasion through epithelial mesenchymal transition (EMT) inhibition via Smad2/3 dependent and independent pathways, suggesting it is an effective therapeutic strategy against HCC metastasis.

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FOXK2 downregulation suppresses EMT in hepatocellular carcinoma

Open Medicine ◽

10.1515/med-2020-0129 ◽

2020 ◽

Vol 15 (1) ◽

pp. 702-708

Author(s):

Jian Kong ◽

Qingyun Zhang ◽

Xuefeng Liang ◽

Wenbing Sun

Keyword(s):

Hepatocellular Carcinoma ◽

Colony Formation ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Endogenous Expression ◽

Forkhead Box ◽

Binding Factor ◽

E Cadherin

AbstractForkhead box K2 (FOXK2) was first identified as an NFAT-like interleukin-binding factor. FOXK2 has been reported to act as either oncogene or tumor suppressor. However, functional and regulating mechanisms of FOXK2 in epithelial–mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. An FOXK2-specific siRNA was employed to decrease the endogenous expression of FOXK2. MTT assay, colony formation and transwell assay were used to evaluate proliferation, migration and invasion of Hep3B and HCCLM3 cells, respectively. The protein expression associated with EMT and Akt signaling pathways was evaluated using western blot. FOXK2 downregulation could inhibit cell proliferation and colony formation and suppress migration and invasion in Hep3B and HCCLM3 cells. The expression of E-cadherin was significantly upregulated, and the expression of snail and p-Akt was significantly downregulated in siFOXK2-transfected cells compared with control cells. SF1670 induced the expression of p-Akt and snail and suppressed the expression of E-cadherin in Hep3B and HCCLM3 cells. SF1670 promoted the invasion and colony formation of Hep3B and HCCLM3 cells. SF1670 partly inhibited the effect of FOXK2 suppression on Hep3B and HCCLM3 cells. In conclusion, this study revealed that FOXK2 downregulation suppressed the EMT in HCC partly through inhibition of the Akt signaling pathway.

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