scholarly journals IL-8 Regulates Epithelial-Mesenchymal Transition through pERK1/2 in AGS Cells

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Torres-Martinez A ◽  
Chavarria C ◽  
Gallardo-Vera F ◽  
Montaño LF ◽  
Rendon-Huerta E
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Ags Cells ◽  
Mesenchymal Transition

scholarly journals Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

2017 ◽  
Vol 42 (3) ◽  
pp. 1025-1036 ◽  
Author(s):  
Dehu Chen ◽  
Guiyuan Liu ◽  
Ning Xu ◽  
Xiaolan You ◽  
Haihua Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Ags Cells ◽  
Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

scholarly journals CLIC4 abrogation promotes epithelial–mesenchymal transition in gastric cancer

2019 ◽  
Vol 41 (6) ◽  
pp. 841-849 ◽  
Author(s):  
Baolong Wang ◽  
Jiqing Zheng ◽  
Qiongyuan Chen ◽  
Chaofan Wu ◽  
Yangxin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Stage ◽  
Stem Cell Markers ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers ◽  
Normal Tissues ◽  
Gastric Adenocarcinomas ◽  
Etoposide Treatment

Abstract Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial–mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.

scholarly journals WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

2016 ◽  
Vol 39 (6) ◽  
pp. 2149-2157 ◽  
Author(s):  
Xiangshu Xian ◽  
Liuye Huang ◽  
Bo Zhang ◽  
Chengrong Wu ◽  
Jun Cui ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cannabis Sativa ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Active Components ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cox 2

Background: Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

scholarly journals Entrectinib Induces Apoptosis and Inhibits the Epithelial–Mesenchymal Transition in Gastric Cancer with NTRK Overexpression

2021 ◽  
Vol 23 (1) ◽  
pp. 395
Author(s):  
Sung-Hwa Sohn ◽  
Hee Jung Sul ◽  
Bum Jun Kim ◽  
Hyeong Su Kim ◽  
Dae Young Zang
Keyword(s):  
Gastric Cancer ◽  
Epithelial Mesenchymal Transition ◽  
High Expression ◽  
Mechanistic Study ◽  
Sequencing Analysis ◽  
Receptor Kinase ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Gastric Cancer Patients

Tropomyosin receptor kinase (TRK) and receptor tyrosine kinase (RTK class VII) expression are important in many human diseases, especially cancers, including colorectal, lung, and gastric cancer. Using RNA sequencing analysis, we evaluated the mRNA expression and mutation profiles of gastric cancer patients with neurotropic tropomyosin receptor kinase (NTRK) 1-3 overexpression (defined as a ≥2.0-fold change). Furthermore, we screened eight TRK inhibitors in NCI-N87, SNU16, MKN28, MKN7, and AGS cells. Among these inhibitors, entrectinib showed the highest inhibitory activity; therefore, this drug was selected for analysis of its therapeutic mechanisms in gastric cancer. Entrectinib treatment induced apoptosis in NTRK1-3-expressing and VEGFR2-expressing NCI-N87 and AGS cells, but it had no effect on NTRK1-3-, VEGFR2-, TGFBR1-, and CD274-expressing MKN7 cells. SNU16 and MKN28 cells with low NTRK1-3 expression were not affected by entrectinib. Therefore, a mechanistic study was conducted in NCI-N87 (high expression of NTRK1-3 but mutation of NTRK3), AGS (high expression of NTRK1-3) and MKN28 (low expression of NTRK1-3) gastric cancer cell lines. Entrectinib treatment significantly reduced expression levels of phosphorylated NFκB, AKT, ERK, and β-catenin in NCI-N87 and AGS cells, whereas it upregulated the expression levels of ECAD in NCI-N87 cells. Together, these results suggest that entrectinib has anti-cancer activity not only in GC cells overexpressing pan NTRK but also in VEGFR2 GC cells via the inhibition of the pan NTRK and VEGFR signaling pathways.

Melittin suppresses epithelial–mesenchymal transition and metastasis in human gastric cancer AGS cells via regulating Wnt/BMP associated pathway

2021 ◽  
Author(s):  
Jye-Yu Huang ◽  
Shu-Fen Peng ◽  
Fu-Shin Chueh ◽  
Po-Yuan Chen ◽  
Yi-Ping Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

ABSTRACT Gastric cancer has a poor prognosis; once cancer has metastasized, it can easily lead to patient death. Melittin is one of the major components extracted from the bee venom. It has been shown that melittin emerges antitumor activities against many human cancer cell lines. Our results indicated that melittin at 0.2-0.5 µm significantly reduced total cell viability in human gastric cancer AGS cells. At low concentrations (0.05-0.15 µm), melittin displayed antimetastasis effects and inhibited cell adhesion and colony formation. Besides, it inhibited cell motility and suppressed cell migration and invasion. Melittin inhibited the activities of MMP-2 and MMP-9 and the integrity of cell membrane in AGS cells. Furthermore, Western blotting results showed that melittin decreased the protein expressions of Wnt/BMP and MMP-2 signaling pathways. Based on these observations, melittin inhibited cell migration and invasion of AGS cells through multiple signaling pathways. It may be used to treat metastasized gastric cancers in the future.

scholarly journals Expression of E-Cadherin in Epithelial Cancer Cells Increases Cell Motility and Directionality through the Localization of ZO-1 during Collective Cell Migration

2021 ◽  
Vol 8 (5) ◽  
pp. 65
Author(s):  
Song-Yi Park ◽  
Hwanseok Jang ◽  
Seon-Young Kim ◽  
Dasarang Kim ◽  
Yongdoo Park ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial–mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

scholarly journals BAP-1 Inhibits Gastric Cancer Progression via PI3K/AKT Pathway by Suppressing FOXK1 Expression

2021 ◽  
Author(s):  
Chen Mi ◽  
Yan Zhao ◽  
Li Ren ◽  
Dan Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Ags Cells ◽  
Mesenchymal Transition

Abstract BRCA1-Associated Protein-1 (BAP-1) gene functions as a vital mediator in tumor formation, progression, and metastasis. The involvement of BAP-1 in colon cancer has been widely reported, but the role of BAP-1 in gastric cancer (GC) is still unclear. In this study, we sought to investigate the contribution of BAP-1 in the pathogenesis of GC. qPCR and Western blot assay were used to detect the mRNA and protein expression of BAP-1 in GC cell lines. MTT and transwell assay were employed to determine the cell viability, migration, and invasion. Annexin V-PI double staining was used to evaluate cell apoptosis. We reported that BAP-1 was expressed at a low level in GC cell lines. Overexpression of BAP-1 inhibited cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) and promoted apoptosis in HGC-27 and AGS cells. BAP-1 inactivated the PI3K/AKT pathway by suppressing Forkhead-box K1 (FOXK1) expression. Moreover, overexpression of FOXK1 reversed the effect of BAP-1 on cell viability, apoptosis, migration, invasion, and EMT. Our data revealed that BAP-1 inhibits cell viability, migration, invasion, and EMT process and promoted apoptosis in HGC-27 and AGS cells through PI3K/AKT pathway via suppressing FOXK1 expression. Thus, BAP-1 can serve as a potential therapeutic target in GC treatment.

scholarly journals Tepotinib Inhibits the Epithelial–Mesenchymal Transition and Tumor Growth of Gastric Cancers by Increasing GSK3β, E-Cadherin, and Mucin 5AC and 6 Levels

2020 ◽  
Vol 21 (17) ◽  
pp. 6027
Author(s):  
Sung-Hwa Sohn ◽  
Hee Jung Sul ◽  
Bohyun Kim ◽  
Bum Jun Kim ◽  
Hyeong Su Kim ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Apoptotic Cell ◽  
Human Gastric Cancer ◽  
Ags Cells ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
E Cadherin

Aberrant expression of mucins (MUCs) can promote the epithelial–mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and β-catenin are associated with MUCs. In this study, we characterized the expression of EMT-relevant proteins including MET, β-catenin, and E-cadherin in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines compared with the c-MET inhibitor tepotinib. We assessed the antitumor activity of tepotinib in GC cell lines. The effects of tepotinib on cell viability, apoptotic cell death, EMT, and c-MET and β-catenin signaling were evaluated by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium (MTS), flow cytometry, Western blotting, and qRT-PCR. The antitumor efficacy was assessed in MKN45 xenograft mice. Tepotinib treatment induced apoptosis in c-MET-amplified SNU620, MKN45, and KATO III cells, but had no effect on c-MET-reduced MKN28 or AGS cells. Tepotinib treatment also significantly reduced the protein levels of phosphorylated and total c-MET, phosphorylated and total ERK, β-catenin, and c-MYC in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expression of EMT-promoting genes such as MMP7, COX-2, WNT1, MUC5B, and c-MYC in c-MET-amplified GC cells and increased the expression of EMT-suppressing genes such as MUC5AC, MUC6, GSK3β, and E-cadherin. In a mouse model, tepotinib exhibited good antitumor growth activity along with increased E-cadherin and decreased phosphorylated c-MET (phospho-c-MET) protein levels. Collectively, these results suggest that tepotinib suppresses tumor growth and migration by negatively regulating c-MET-induced EMT. These findings provide new insights into the mechanism by which MUC5AC and MUC6 contribute to GC progression.

scholarly journals LncRNA HCP5 Induces Gastric Cancer Cell Proliferation, Invasion, and EMT Processes Through the miR-186-5p/WNT5A Axis Under Hypoxia

2021 ◽  
Vol 9 ◽  
Author(s):  
Ming Gao ◽  
Liying Liu ◽  
Yudan Yang ◽  
Mengyi Li ◽  
Qingqing Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Pearson Correlation ◽  
Luciferase Reporter ◽  
Protein Markers ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Wnt5a Expression ◽  
Gastric Cancer Cell Proliferation

ObjectiveTo experimentally determine the involvement and mechanism of long non-coding RNA (lncRNA) HCP5 in the development of gastric cancer (GC).MethodsDetection of HCP5, miR-186-5p, and WNT5A expression in clinical GC tissues and adjacent healthy tissues was performed, followed by Pearson correlation analysis. BGC-823 and AGS cells, with interferences of HCP5, miR-186-5p, and WNT5A, were cultured under hypoxia. MTT, colony formation assay, Caspase-3 activity assay, and transwell assay were applied for the determination of cell proliferation, viability, apoptosis, and invasion, respectively. Expressions of WNT5A and protein markers of epithelial-mesenchymal transition (EMT) in cells were detected by western blotting. And the binding of HCP5 and WNT5A to miR-186-5p was validated using dual-luciferase reporter assay.ResultsIn GC tissues, an increase in HCP5 and WNT5A expressions and a reduction in miR-186-5p expression were found, and the negative correlation between miR-186-5p and HCP5/WNT5A was proven. Subsequently, under hypoxia, an increase in HCP5 and WNT5A expressions and a decrease in miR-186-5p expression in GC cells were confirmed. In addition, in GC cells under hypoxia, the inhibition of HCP5 suppressed cell biological activity and EMT, while the inhibition of miR-186-5p or the overexpression of WNT5A led to the opposite changes.ConclusionAn upregulation of WNT5A expression by HCP5 competitively binding to miR-186-5p promotes GC cell development.

scholarly journals Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter

2014 ◽  
Vol 52 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Lin Xiao ◽  
Suzana Kovac ◽  
Mike Chang ◽  
Arthur Shulkes ◽  
Graham S Baldwin ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Significant Stimulation ◽  
E Box ◽  
Human Gastric Adenocarcinoma

Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn2+ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55±14-fold at 100 μM (P<0.05). Significant stimulation was also observed with Cd2+and Cu2+, but not with Ca2+, Mg2+, Ni2+, or Fe3+ions. Activation of MAPK and phosphatidylinositol 3-kinase pathways is necessary but not sufficient for gastrin induction by Zn2+. Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn2+-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial–mesenchymal transition (EMT), together with our observation that Zn2+ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn2+ions may induce an EMT, and that gastrin may be involved in the transition.

Sign in / Sign up

Export Citation Format

Share Document