scholarly journals F806 Suppresses the Invasion and Metastasis of Esophageal Squamous Cell Carcinoma via Downregulating F-Actin Assembly-Related Rho Family Proteins

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Lei Xie ◽  
Li-Yan Li ◽  
Duo Zheng ◽  
Yang-Min Xie ◽  
Xiu-E Xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Small Gtpase ◽  
Actin Assembly ◽  
Invasion And Metastasis ◽  
Cancer Migration ◽  
Rho Family ◽  
Rho Family Proteins

Invasion and metastasis are critical pathological and mortal processes in esophageal squamous cell carcinoma (ESCC). Novel drugs, targeting the two cancer migration stages, will augment the treatment options for ESCC therapy and improve overall survival. A novel natural macrolide F806 specifically promotes apoptosis of various ESCC cells. However, whether F806 can inhibit metastasis of ESCC cells needs further evaluation. Here, our data showed that F806 inhibits dynamic F-actin assembly and then suppresses the migration of ESCC cells in vitro and their invasion and metastasis in vivo. The correlation between cancer migration and actin cytoskeleton assembly was consistent with the ability of F806 to prevent the aggregation of Paxillin, an essential protein for focal adhesion formation through binding to the ends of actin filaments. Furthermore, F806 downregulated the expression and activity of the Rho family proteins cell division cycle 42 (CDC42), RAC family small GTPase 1 (RAC1), and RAS homolog family member A (RHOA). Taken together, these results suggest that F806 can suppress cancer invasion and metastasis via interrupting the assembly of migration components involving F-actin.

scholarly journals RNF128 Promotes Invasion and Metastasis Via the EGFR/MAPK/MMP-2 Pathway in Esophageal Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 840 ◽  
Author(s):  
Jing Gao ◽  
Yang Wang ◽  
Jie Yang ◽  
Weixia Zhang ◽  
Kun Meng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ring Finger ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Invasion And Metastasis ◽  
Nude Mouse Model ◽  
Invasion And Migration

Background: The prognosis of esophageal squamous cell carcinoma (ESCC) is generally poor, and the identification of molecular markers related to the regulation of ESCC invasion and migration is important. Methods and Results: In this study, we report that ring finger protein-128 (RNF128) enhances the invasiveness and motility of ESCC cells by using transwell assays and Western blotting. A xenograft nude mouse model showed that RNF128 promotes the metastasis of ESCC cells in the lung. A signal pathway analysis identified the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/matrix matalloproteinases 2 (MMP-2) cascade as a mediator of RNF128-induced enhancement of ESCC progression. Inhibition experiments using inhibitors of EGFR, ERK kinase (MEK)/extracellular-signal-regulated-kinase (ERK), and MMP-2 reversed this progression. Co-immunoprecipitation demonstrated that RNF128 promotes the activation of the EGFR/ERK/MMP-2 pathway by interacting with p53 and p53 interacting with EGFR. Conclusion: Our results establish the functional role of RNF128 in driving the invasion and metastasis of ESCC through the EGFR/MAPK/MMP-2 pathway, implicating its potential as a candidate therapeutic target and prognostic biomarker for ESCC.

scholarly journals HLA-DR regulates macrophage phenotypic transformation and affects malignant behavior in esophageal squamous cell carcinoma

2020 ◽  
Author(s):  
Jiang Fen Li ◽  
Yu Fang Xie ◽  
Wei Hua Liang ◽  
Hai Jun Zhang ◽  
Xue Li Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Macrophage Polarization ◽  
Biological Behavior ◽  
Invasion And Metastasis ◽  
Hla Dr ◽  
Low Expression

Abstract Background Tumor-associated macrophages (TAMs) are an important immune cell component of the tumor microenvironment. This study aimed to explore the molecular mechanism of TAMs phenotype transformation and the role in the development of esophageal squamous cell carcinoma (ESCC).Methods Co-culture conditions were employed to determine the phenotypic effects of TAMs on ESCC cell biological behavior. Tumor metastasis related molecules VEGF-C and MMP-9 produced by TAMs was evaluated by qRT-PCR and western blot. Expression of HLA-DR was knocked down in TAMs in vitro to determine the effects on macrophage polarization and the biological behavior of ESCC. We determined whether co-injection with M2 TAMs and macrophages depletion affected tumor growth in vivo tumor challenge model. Associations between HLA-DR, TAM density, and clinical outcomes were evaluated in patients with ESCC.Results TAMs in ESCC samples were found to closely reflect the M2 phenotype of TAMs, and exhibited low expression of HLA-DR. Which was involved in ESCC tumor invasion and metastasis. Low expression of HLA-DR positively correlated with high-density of M2 TAMs, indicating high invasiveness and poor prognosis in patients with ESCC. Downregulation of HLA-DR in TAMs led to additional M2-type TAM polarization and more VEGF-C and MMP-9 secretion, promoted the malignant transformation of ESCC.Conclusions These results demonstrate that downregulation of HLA-DR promote the transformation of M2 TAMs, and participate in the invasion and metastasis of ESCC.

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