Malic enzyme 1 induces epithelial–mesenchymal transition and indicates poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial–mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

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Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition

Hepatology ◽

10.1002/hep.28417 ◽

2016 ◽

Vol 63 (4) ◽

pp. 1256-1271 ◽

Cited By ~ 56

Author(s):

Shuai Xiao ◽

Rui-Min Chang ◽

Ming-Yang Yang ◽

Xiong Lei ◽

Xiao Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling

Clinical Science ◽

10.1042/cs20190225 ◽

2019 ◽

Vol 133 (14) ◽

pp. 1645-1662 ◽

Cited By ~ 7

Author(s):

Yan-rong Zhao ◽

Ji-long Wang ◽

Cong Xu ◽

Yi-ming Li ◽

Bo Sun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Heart Development ◽

Poor Prognosis ◽

Nuclear Translocation ◽

Epithelial Mesenchymal Transition ◽

Disease Free Survival ◽

Intrahepatic Metastasis ◽

Mesenchymal Transition

Abstract Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial–mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo. Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes β-catenin expression and maintains its stability, leading to intracellular β-catenin accumulation, β-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that β-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/β-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.

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SYPL1 overexpression predicts poor prognosis of hepatocellular carcinoma and associates with epithelial-mesenchymal transition

Oncology Reports ◽

10.3892/or.2017.5843 ◽

2017 ◽

Vol 38 (3) ◽

pp. 1533-1542 ◽

Cited By ~ 7

Author(s):

Dong-Han Chen ◽

Qiu-Wan Wu ◽

Xiu-Dong Li ◽

Shuang-Jia Wang ◽

Zhi-Ming Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis

Journal of Oncology ◽

10.1155/2020/1980368 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yixi Zhang ◽

Xiaojing Luo ◽

Jianwei Lin ◽

Shunjun Fu ◽

Pei Feng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Progression ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Disease Free Survival ◽

Tumour Cells ◽

Migration And Invasion ◽

Mesenchymal Transition

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, P<0.001) and DFS (HR = 1.744, 95% CI = 1.205–2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.

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IQGAP1 expression in hepatocellular carcinoma predicts poor prognosis by inducing epithelial-mesenchymal transition

Translational Cancer Research ◽

10.21037/tcr.2017.05.40 ◽

2017 ◽

Vol 6 (3) ◽

pp. 530-540 ◽

Cited By ~ 2

Author(s):

Chuan Li ◽

Tian-Fu Wen ◽

Xiao-Yun Zhang ◽

Xiang Chen ◽

Jun-Yi Shen

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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RETRACTED ARTICLE: Sorcin Predicts Poor Prognosis and Promotes Metastasis by Facilitating Epithelial-mesenchymal Transition in Hepatocellular Carcinoma

Scientific Reports ◽

10.1038/s41598-017-10365-3 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Xiong Lei ◽

Yahang Liang ◽

Jian Chen ◽

Shuai Xiao ◽

Jian Lei ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Significant Risk ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Multiple Tumor ◽

Liver Tissues

Abstract Metastasis-associated recurrence is the main cause for the poor prognosis of hepatocellular carcinoma (HCC). However, the detailed molecular mechanisms underlying HCC metastasis remain elusive. Though some data indicated the oncogenic role of Sorcin in tumors, the prognostic value and biological role of Sorcin in HCC is still unknown. In this study, it demonstrated that Sorcin expression levels were significantly upregulated in HCC tumor tissues compared with matched adjacent nontumorous liver tissues and normal liver tissues, and such expression level correlated with HCC metastasis. High Sorcin expression was significantly correlated with aggressive clinicopathological characteristics such as multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05). HCC patients with high Sorcin expression had both shorter survival and higher recurrence than those with low Sorcin expression (all P < 0.05). Sorcin expression was an independent and significant risk factor for survival and recurrence of HCC patients. Results of functional experiments showed that Sorcin could promote HCC cell proliferation, migration, and invasion in vitro, and facilitate HCC growth and metastasis in vivo. Mechanistically, Sorcin exerted its role by activating extracellular signal-regulated kinase (ERK) pathway and promoted metastasis by facilitating epithelial-mesenchymal transition (EMT) in HCC.

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