Deubiquitinase USP13 promotes the epithelial-mesenchymal transition and metastasis in gastric cancer by maintaining Snail protein

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

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A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02329-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wanting Song ◽

Yi Bai ◽

Jialin Zhu ◽

Fanxin Zeng ◽

Chunmeng Yang ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Risk Model ◽

Cox Regression ◽

Epithelial Mesenchymal Transition ◽

Risk Groups ◽

The Cancer Genome Atlas ◽

Critical Function ◽

Mesenchymal Transition ◽

Patient Prognosis

Abstract Background Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. Methods Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. Results Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. Conclusions We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

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Adapting and Surviving: Intra and Extra-Cellular Remodeling in Drug-Resistant Gastric Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20153736 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3736 ◽

Cited By ~ 12

Author(s):

Sabino Russi ◽

Henu Kumar Verma ◽

Simona Laurino ◽

Pellegrino Mazzone ◽

Giovanni Storto ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Epithelial Mesenchymal Transition ◽

Current Approach ◽

Gastric Cancer Cells ◽

Drug Induced ◽

Cytotoxic Effects ◽

Mesenchymal Transition ◽

Damage Response ◽

Drug Detoxification

Despite the significant recent advances in clinical practice, gastric cancer (GC) represents a leading cause of cancer-related deaths in the world. In fact, occurrence of chemo-resistance still remains a daunting hindrance to effectiveness of the current approach to GC therapy. There is accumulating evidence that a plethora of cellular and molecular factors is implicated in drug-induced phenotypical switching of GC cells. Among them, epithelial-mesenchymal transition (EMT), autophagy, drug detoxification, DNA damage response and drug target alterations, have been reported as major determinants. Intriguingly, resistant GC phenotype may be the result of GC cell-induced tumor microenvironment (TME) remodeling, which is currently emerging as a key player in promoting drug resistance and overcoming cytotoxic effects of drugs. In this review, we discuss the possible mechanisms of drug resistance and their involvement in determining current GC therapies failure.

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Inflammatory microenvironment contributes to epithelial-mesenchymal transition in gastric cancer

World Journal of Gastroenterology ◽

10.3748/wjg.v22.i29.6619 ◽

2016 ◽

Vol 22 (29) ◽

pp. 6619 ◽

Cited By ~ 20

Author(s):

Hui-Ying Ma ◽

Xin-Zhou Liu ◽

Chun-Min Liang

Keyword(s):

Gastric Cancer ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Inflammatory Microenvironment

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MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

Molecular Biology of the Cell ◽

10.1091/mbc.e09-05-0386 ◽

2009 ◽

Vol 20 (24) ◽

pp. 5127-5137 ◽

Cited By ~ 27

Author(s):

Kai-Wen Hsu ◽

Rong-Hong Hsieh ◽

Chew-Wun Wu ◽

Chin-Wen Chi ◽

Yan-Hwa Wu Lee ◽

...

Keyword(s):

Gastric Cancer ◽

Tumor Progression ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Suppressive Effect ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Mesenchymal Transition ◽

Cox 2

The c-Myc promoter binding protein 1 (MBP-1) is a transcriptional suppressor of c-myc expression and involved in control of tumorigenesis. Gastric cancer is one of the most frequent neoplasms and lethal malignancies worldwide. So far, the regulatory mechanism of its aggressiveness has not been clearly characterized. Here we studied roles of MBP-1 in gastric cancer progression. We found that cell proliferation was inhibited by MBP-1 overexpression in human stomach adenocarcinoma SC-M1 cells. Colony formation, migration, and invasion abilities of SC-M1 cells were suppressed by MBP-1 overexpression but promoted by MBP-1 knockdown. Furthermore, the xenografted tumor growth of SC-M1 cells was suppressed by MBP-1 overexpression. Metastasis in lungs of mice was inhibited by MBP-1 after tail vein injection with SC-M1 cells. MBP-1 also suppressed epithelial-mesenchymal transition in SC-M1 cells. Additionally, MBP-1 bound on cyclooxygenase 2 (COX-2) promoter and downregulated COX-2 expression. The MBP-1-suppressed tumor progression in SC-M1 cells were through inhibition of COX-2 expression. MBP-1 also exerted a suppressive effect on tumor progression of other gastric cancer cells such as AGS and NUGC-3 cells. Taken together, these results suggest that MBP-1–suppressed COX-2 expression plays an important role in the inhibition of growth and progression of gastric cancer.

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