MEG3 affects the progression and chemoresistance of T‐cell lymphoblastic lymphoma by suppressing epithelial‐mesenchymal transition via the PI3K/mTOR pathway

2018 ◽  
Vol 120 (5) ◽  
pp. 8144-8153 ◽  
Author(s):  
Rui Deng ◽  
Fang‐Yi Fan ◽  
Hai Yi ◽  
Fang Liu ◽  
Guang‐Cui He ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mtor Pathway ◽  
Lymphoblastic Lymphoma ◽  
Mesenchymal Transition

scholarly journals Correction to: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Betacatenin/FOXG1 complex

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xingrong Zheng ◽  
Jiaxin Lin ◽  
Hewei Wu ◽  
Zhishuo Mo ◽  
Yunwen Lian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
T Cell Factor ◽  
Forkhead Box ◽  
Wnt Signal

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals The Expression of TRIM6 Activates the mTORC1 Pathway by Regulating the Ubiquitination of TSC1-TSC2 to Promote Renal Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Weiwei Liu ◽  
Yang Yi ◽  
Chuanfu Zhang ◽  
Baojuan Zhou ◽  
Lin Liao ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Mtor Pathway ◽  
Mesenchymal Transition ◽  
Regulatory Pathways ◽  
Mtorc1 Pathway ◽  
Hk2 Cells

Renal fibrosis is considered as the final pathway of all types of kidney diseases, which can lead to the progressive loss of kidney functions and eventually renal failure. The mechanisms behind are diversified, in which the mammalian target of rapamycin (mTOR) pathway is one of the most important regulatory pathways that accounts for the disease. Several processes that are regulated by the mTOR pathway, such as autophagy, epithelial-mesenchymal transition (EMT), and endoplasmic reticulum (ER) stress, are tightly associated with renal fibrosis. In this study, we have reported that the expression of tripartite motif-containing (TRIM) protein 6, a member of TRIM family protein, was highly expressed in renal fibrosis patients and positively correlated with the severity of renal fibrosis. In our established in vitro and in vivo renal fibrosis models, its expression was upregulated by the Angiotensin II-induced nuclear translocation of nuclear factor-κB (NF-κB) p50 and p65. In HK2 cells, the expression of TRIM6 promoted the ubiquitination of tuberous sclerosis proteins (TSC) 1 and 2, two negative regulators of the mTORC1 pathway. Moreover, the knockdown of TRIM6 was found efficient for alleviating renal fibrosis and inhibiting the downstream processes of EMT and ER in both HK2 cells and 5/6-nephrectomized rats. Clinically, the level of TRIM6, TSC1/2, and NF-κB p50 was found closely related to renal fibrosis. As a result, we have presented the first study on the role of TRIM6 in the mTORC1 pathway in renal fibrosis models and our findings suggested that TRIM6 may be a potential target for the treatment of renal fibrosis.

scholarly journals Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Xingrong Zheng ◽  
Jiaxin Lin ◽  
Hewei Wu ◽  
Zhishuo Mo ◽  
Yunwen Lian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Nuclear Accumulation ◽  
Beta Catenin ◽  
Mesenchymal Transition ◽  
T Cell Factor ◽  
Forkhead Box

Abstract Background Forkhead box G1 (FOXG1) is a member of the Fox transcription factor family involved in regulation of many cancers. However, the role of FOXG1 in hepatocellular carcinogenesisis largely unclear. The present study aimed at examining the biological function and underlying mechanism of FOXG1 on hepatocellular carcinoma (HCC) tumor metastasis as well as its clinical significance. Methods Levels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in HCC cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. Immunoprecipitation and chromatin immunoprecipitation assays were performed to investigate the interaction of FOXG1, β-catenin, TCF4 and the effect on Wnt target-gene promoters. Results In human HCC, the level of FOXG1 progressively increased from surrounding non tumorous livers to HCC, reaching the highest levels in metastatic HCC. Furthermore, expression levels of FOXG1 directly correlated with cancer cell epithelial-mesenchymal transition (EMT) phenotype. In FOXG1-overexpressing cells, FOXG1 promotes the stabilization and nuclear accumulation of β-catenin by directly binding to β-catenin and it associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) on Wnt responsive enhancers (WREs) in chromatin. Conclusions The results show that FOXG1 plays a key role in mediating cancer cell metastasis through the Wnt/β-catenin pathway in HCC cells and predicts HCC prognosis after surgery. Targeting FOXG1 may provide a new approach for therapeutic treatment in the future.

scholarly journals p53-Mediated PI3K/AKT/mTOR Pathway Played a Role in PtoxDpt-Induced EMT Inhibition in Liver Cancer Cell Lines

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Yongli Li ◽  
Tingting Wang ◽  
Yanjie Sun ◽  
Tengfei Huang ◽  
Cuiping Li ◽  
...  
Keyword(s):  
Topoisomerase Ii ◽  
Epithelial Mesenchymal Transition ◽  
Iron Chelator ◽  
Significant Inhibition ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Liver Cancer Cell ◽  
Wild Type ◽  
Structural Units ◽  
Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) involves metastasis and drug resistance; thus, a new EMT reversing agent is required. It has shown that wild-type p53 can reverse EMT back to epithelial characteristics, and iron chelator acting as a p53 inducer has been demonstrated. Moreover, recent study revealed that etoposide could also inhibit EMT. Therefore, combination of etoposide with iron chelator might achieve better inhibition of EMT. To this end, we prepared di-2-pyridineketone hydrazone dithiocarbamate S-propionate podophyllotoxin ester (PtoxDpt) that combined the podophyllotoxin (Ptox) structural unit (etoposide) with the dithiocarbamate unit (iron chelator) through the hybridization strategy. The resulting PtoxDpt inherited characteristics from parent structural units, acting as both the p53 inducer and topoisomerase II inhibitor. In addition, the PtoxDpt exhibited significant inhibition in migration and invasion, which correlated with downregulation of matrix metalloproteinase (MMP). More importantly, PtoxDpt could inhibit EMT in the absence or presence of TGF-β1, concomitant to the ROS production, and the additional evidence revealed that PtoxDpt downregulated AKT/mTOR through upregulation of p53, indicating that PtoxDpt induced EMT inhibition through the p53/PI3K/AKT/mTOR pathway.

scholarly journals Discovery and Validation of an Epithelial-Mesenchymal Transition-Based Signature in Gastric Cancer by Genomics and Prognosis Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-35
Author(s):  
Huiyong Xu ◽  
Huilai Wan ◽  
Maoshu Zhu ◽  
Lianghua Feng ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cell ◽  
Cox Regression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Cell Cancer ◽  
External Validation ◽  
Receptor Interaction ◽  
Related Gene ◽  
Mesenchymal Transition

Objective. Epithelial-mesenchymal transition (EMT) exerts a key function in cancer initiation and progression. Herein, we aimed to develop an EMT-based prognostic signature in gastric cancer. Methods. The gene expression profiles of gastric cancer were obtained from TCGA dataset as a training set and GSE66229 and GSE84437 datasets as validation sets. By LASSO regression and Cox regression analyses, key prognostic EMT-related genes were screened for developing a risk score (RS) model. Potential small molecular compounds were predicted by the CMap database based on the RS model. GSEA was employed to explore signaling pathways associated with the RS. ESTIMATE and seven algorithms (TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC) were applied to assess the RS and immune microenvironment. Results. This study developed an EMT-related gene signature comprised of SERPINE1, PCOLCE2, MATN3, and DKK1. High-RS patients displayed poorer survival outcomes than those with low RS. ROC curves demonstrated the robustness of the model in predicting the prognosis. After external validation, the RS model was an independent risk factor for gastric cancer. Several compounds were predicted for gastric cancer treatment based on the RS model. ECM receptor interaction, focal adhesion, pathway in cancer, TGF-beta, and WNT pathways were distinctly activated in high-RS samples. Also, high RS was significantly associated with increased stromal and immune scores and increased infiltration of CD4+ T cell, CD8+ T cell, cancer-associated fibroblast, and macrophage in gastric cancer tissues. Conclusion. Our findings suggested that the EMT-related gene model may robustly predict gastric cancer prognosis, which could improve the efficacy of personalized therapy.

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