scholarly journals TGF-β1/Smad Signaling Pathway Regulates Epithelial-to-Mesenchymal Transition in Esophageal Squamous Cell Carcinoma: In Vitro and Clinical Analyses of Cell Lines and Nomadic Kazakh Patients from Northwest Xinjiang, China

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e112300 ◽  
Author(s):  
Lijuan Pang ◽  
Qiuxiang Li ◽  
Cuilei Wei ◽  
Hong Zou ◽  
Shugang Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling Pathway ◽  
Tgf Β1

scholarly journals ATAD2 interacts with C/EBPβ to promote esophageal squamous cell carcinoma metastasis via TGF-β1/Smad3 signaling

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Lian-Jing Cao ◽  
Yi-Jun Zhang ◽  
Si-Qi Dong ◽  
Xi-Zhao Li ◽  
Xia-Ting Tong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Squamous Cell ◽  
Downstream Effectors ◽  
Tgf Β1

Abstract Background Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated. Methods The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay. Results We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPβ. ATAD2 directly interacted with C/EBPβ and promoted its nuclear translocation, which directly bound to the promoter region of TGF-β1 and activated its expression. Further, we demonstrated that TGF-β1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-β signaling induced Snail expression and the subsequent epithelial-mesenchymal transition. Conclusion Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPβ/TGF-β1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.

scholarly journals Gremlin1 Delivered by Mesenchymal Stromal Cells Promoted Epithelial-Mesenchymal Transition in Human Esophageal Squamous Cell Carcinoma

2018 ◽  
Vol 47 (5) ◽  
pp. 1785-1799 ◽  
Author(s):  
Dongxi Hong ◽  
Te Liu ◽  
Weijun Huang ◽  
Yan Liao ◽  
Lin Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

Backgroud/Aims: Mesenchymal stromal cells (MSCs) are a major component of the tumor microenvironment (TME). Several studies focusing on tumor-derived MSCs have demonstrated that they exhibit a strong ability to promote the tumor epithelial-mesenchymal transition (EMT). However, the factors mediating these effects are poorly understood. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry assays were used to detect the expression of Gremlin1 (GREM1) in human esophageal squamous cell carcinoma (ESCC) tissues. ShRNA silencing, flow cytometry, cell counting kit (CCK8) assay, invasion assay, western blot were used to detect the effect of GREM1 in ECa109, TE-1 cell lines and xenograft tumor models. Results: In the current study, we found that the GREM1 was overexpressed in human ESCC tissues. The conditioned medium from mesenchymal stromal cells (MSCs-CM) enhanced the malignancy of xenograft esophageal tumors in vivo, as well as the cell proliferation, viability and invasion of the esophageal carcinoma cell lines ECa109 and TE-1 in vitro. Furthermore, the shRNA silencing of GREM1 in MSCs (shGREM1-MSCs) reversed the increased malignancy of the esophageal tumor in vivo, while the conditioned medium from shGREM1-MSCs (shGREM1-MSCs-CM) affected the cell cycle and cell invasion in vitro. These processes were accompanied by the EMT in the ECa109 and TE-1 cell lines with an alteration in the expression levels of mesenchymal and epithelial markers. Furthermore, the TGF-β/BMP (transforming growth factor-beta/bone morphogenetic protein) signaling pathway participated in the shGREM1-MSCs-CM-induced anti-tumor effect on enhanced esophageal malignancy induced by MSCs-CM treatment. Conclusions: Taken together, our study suggested that GREM1 delivered by MSCs promoted EMT in ESCC in vitro and in vivo, which is partly through TGF-β/BMP signaling pathway. The results provide experimental evidence to a potential therapeutic target in the treatment of esophageal cancer.

(S,R)3-(4-Hydroxyphenyl)-4,5-Dihydro-5-Isoxazole Acetic Acid Methyl Ester Inhibits Epithelial-to-Mesenchymal Transition through TGF-β/Smad4 Axis in Nasopharyngeal Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Qibing Chen ◽  
Yan Wang ◽  
Fen Li ◽  
Xiang Cheng ◽  
Yu Xiao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Nasopharyngeal Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Immunofluorescence Assay ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background: Macrophage migration inhibitory factor (MIF), originally reported as an inflammation regulating molecule, is elevated in various cancer cells, which may promote carcinogenesis. Meanwhile, ISO-1 is a potent small molecular inhibitor of MIF, which has not been investigated in nasopharyngeal carcinoma (NPC); hence the impact of ISO-1 on NPC cells remains to be illustrated. Objective: This study intended to explore the biological function of ISO-1 in NPC cells in vitro and prove a possibility of ISO-1 being a novel agent in NPC treatments. Methods: Gene expression of MIF in Head and Neck squamous cell carcinoma were obtained from The Cancer Genome Atlas (TCGA) database. Nasal pharyngeal tissues were collected from adult patients undergoing nasopharyngeal biopsy for MIF level detection. Proliferation of NPC cell lines 5-8B and 6-10B was studied using Cell Counting Kit-8 (CCK-8) assay and plate-colony-formation assay, apoptosis was determined by flow cytometry and TUNEL staining, migration and invasion capacities were measured by wound-healing assay and transwell assay, all to explore the function of ISO-1 in NPC cells in vitro. Epithelial-to-mesenchymal transition (EMT) level of NPC cells was determined by Western blot analysis and immunofluorescence assay. Results: Transcript level of MIF was significantly higher in head and neck squamous cell carcinoma. Protein MIF was overexpressed in human NPC tissues compared to non-cancerous ones, and its expression could be compromised by ISO-1 in vitro. 100μM ISO-1 significantly hindered NPC cells migration and invasion capacities in vitro but acted relatively poorly on proliferation and apoptosis. Immunofluorescence assay and Western blotting implied a down-regulated EMT level through TGF-β/Smad4 axis in ISO-1 treated NPC cells compared to the vehicle. Conclusion: This study indicated that MIF antagonist ISO-1 holds impact on NPC progression by influencing the migration and invasion of NPC cells ISO-1 inhibits the EMT process of NPC cells through TGF-β/Smad4 axis, supporting that prudent application of ISO-1 may be a potential adjuvant treatment for NPC.

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