scholarly journals MEGF6 Promotes the Epithelial-to-Mesenchymal Transition via the TGFβ/SMAD Signaling Pathway in Colorectal Cancer Metastasis

2018 ◽  
Vol 46 (5) ◽  
pp. 1895-1906 ◽  
Author(s):  
Hanqing Hu ◽  
Meng Wang ◽  
Hongwei Wang ◽  
Zheng Liu ◽  
Xu Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Growth Factor ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Background/Aims: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFβ)/SMAD signaling pathway. Methods: RNA sequencing data from the Gene Expression Omnibus database were analyzed using R software. Based on The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) cohort, the clinical significance of MEGF6 was investigated. HCT8R, HCT116, and LoVo CRC cells were transfected with small interfering RNA against MEGF6, and their proliferation and sensitivity to fluorouracil were evaluated with the MTT cell proliferation and colony formation assays. Proteins associated with cell growth were detected by western blot analysis. The apoptosis of cells was evaluated by Annexin V/propidium iodide staining, and transwell assays were performed to assess the involvement of MEGF6 in cell migration. Markers of EMT and TGFβ/SMAD signaling were evaluated by quantitative PCR and western blotting, and the correlation between MEGF6 and these markers was assessed in the TCGA colon and renal adenocarcinoma cohort. Results: The results showed that MEGF6 was upregulated in HCT8R cells. In addition, MEGF6 was significantly overexpressed in tumor tissue and predicted a poor survival in the TCGA-COAD cohort. Moreover, MEGF6 accelerated CRC cell growth and inhibited apoptosis, and promoted CRC metastasis by inducing the EMT. Finally, we found that TGFβ/SMAD signaling triggered the expression of Slug, which regulates the MEGF6-mediated EMT. Conclusions: MEGF6 may serve as an oncogene to promote cell proliferation and inhibit apoptosis. MEGF6 can also accelerate cell migration via TGFβ/SMAD signaling-mediated EMT.

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

scholarly journals Effects of Astragaloside IV Against the TGF-β1-Induced Epithelial-to-Mesenchymal Transition in Peritoneal Mesothelial Cells by Promoting Smad 7 Expression

2015 ◽  
Vol 37 (1) ◽  
pp. 43-54 ◽  
Author(s):  
Lu Zhang ◽  
Zhenghong Li ◽  
Weiming He ◽  
Lingdong Xu ◽  
Jing Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Treated Group ◽  
Mesothelial Cells ◽  
Vehicle Group ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Peritoneal Mesothelial Cells ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Background/Aims: To investigate the effect of Astragaloside IV (AS-IV) on the regulation of the TGF-β1/Smad signaling pathway in peritoneal mesothelial cells with an epithelial-to-mesenchymal transition (EMT). Methods: EMT of human peritoneal mesothelial cells (HMrSV5) was induced using 2 ng/ml TGF-β1. Cells were randomly divided into a vehicle group, a vehicle group with AS-IV, a TGF-β1 treated group, and a TGF-β1 treated group receiving varied doses of AS-IV or NAC. Real-time quantitative PCR and western blot were used to detect the expression of genes and proteins associated with the TGF-β1/Smad signaling pathway and EMT. DCFH-DA was used to detect the generation of ROS in HMrSV5 cells, and a transwell migration assay was used to verify the capacity of AS-IV to inhibit EMT in HMrSV5 cells. Lentiviruses were used as carriers for the overexpression or knockdown of the Smad7 gene. Results: Expression levels of E-cadherin (epithelial marker) was decreased and vimentin, α-SMA (EMT markers) and collagen I (extracellular matrix protein) phospho-Smad2/3, Snail1 and Snail2 was increased significantly in the TGF-β1-treated HMrSV5 cells. AS-IV was associated with downregulated expression of vimentin and phospho-Smad2/3 in a dose-dependent manner, while the expression of Smad7 increased. Silenced or forced expression of Smad7 verified its role in the inhibitory effect of AS-IV on TGF-β1-induced EMT in HMrSV5 cells. Conclusion: AS-IV effectively promotes the upregulation of Smad7 in the TGF-β1/Smad signaling pathway during the EMT of HMrSV5 cells, indicating its potential therapeutic effect for the control of PF.

scholarly journals Bleomycin (BLM) Induces Epithelial-to-Mesenchymal Transition in Cultured A549 Cells via the TGF-β/Smad Signaling Pathway

2016 ◽  
Vol 7 (11) ◽  
pp. 1557-1564 ◽  
Author(s):  
Kui-Jun Chen ◽  
Qing Li ◽  
Cang-mei Wen ◽  
Zhao-Xia Duan ◽  
Jie yuan Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals The Overexpression of Keratin 23 Promotes Migration of Ovarian Cancer via Epithelial-Mesenchymal Transition

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Meng Ren ◽  
Yan Gao ◽  
Qi Chen ◽  
Hongyu Zhao ◽  
Xiaoting Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Background. Keratin 23 (KRT23) is a new member of the KRT gene family and known to be involved in the development and migration of various types of tumors. However, the role of KRT23 in ovarian cancer (OC) remains unclear. This study is aimed at investigating the function of KRT23 in OC. Methods. The expression of KRT23 in normal ovarian and OC tissues was determined using the Oncomine database and immunohistochemical staining. Reverse transcription quantitative polymerase chain reaction assay was used to analyze the expression of KRT23 in normal ovarian epithelial cell lines and OC cell lines. Small interfering RNA (siRNA), wound healing assay, and transwell assay were conducted to detect the effects of KRT23 on OC cell migration and invasion. Further mechanistic studies were verified by the Gene Expression Profiling Interactive Analysis platform, Western blotting, and immunofluorescence staining. Results. KRT23 was highly expressed in OC tissues and cell lines. High KRT23 expression could regulate OC cell migration and invasion, and the reduction of KRT23 by siRNA inhibited the migration and invasion of OC cells in vitro. Furthermore, KRT23 mediated epithelial-mesenchymal transition (EMT) by regulating p-Smad2/3 levels in the TGF-β/Smad signaling pathway. Conclusions. These results demonstrate that KRT23 plays an important role in OC migration via EMT by regulating the TGF-β/Smad signaling pathway.

scholarly journals TGFβ1-Smad Signaling Pathway Participates in Interleukin-33 Induced Epithelial-to-Mesenchymal Transition of A549 Cells

2018 ◽  
Vol 50 (2) ◽  
pp. 757-767 ◽  
Author(s):  
Qiu-Yue Tan ◽  
Zhen-Shun  Cheng
Keyword(s):  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Control Group ◽  
Western Blot Assay ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Interleukin 33 ◽  
Smad Signaling Pathway ◽  
Receptor Inhibitor

Backgrounds/Aims: Epithelial-to-mesenchymal transition (EMT) has been proven to be involved in development and progression of pulmonary fibrosis. This study aims to investigate the role of transforming growth factor β1 (TGFβ1)-smad signaling pathway in the interleukin-33 (IL-33) induced EMT. Methods: The human type II alveolar epithelial cell line, A549, and small airway epithelial cells (SAEC) were cultured and divided into 4 groups including Control, LY-2109761 (TGFβ receptor inhibitor), IL-33 and IL-33+LY-2109761 group. Expression of TGFβ1, E-cadherin (E-cad) and α-smooth muscle actin (α-SMA) were examined by using real-time PCR (RT-PCR) and western blot assay, respectively. The smad3 signaling pathway factors, including smad3 and phosphorylated smad3 (p-smad3), were also detected by using western blot assay. Results: IL-33 significantly activated T1/ST2 expression in A549 cells (P< 0.05). TGFβ1 receptor inhibitor significantly suppressed the IL-33 caused down-expression of E-cad compared to IL-33 alone (P< 0.05). IL-33 significantly increased the α-SMA levels compared to Control group (P< 0.05) and TGFβ1 receptor inhibitor inhibited the other effects of IL-33. IL-33 significantly enhanced the levels of TGFβ1 compared to Control group (P< 0.05). TGFβ1 receptor inhibitor suppressed the IL-33 induced up-expression of p-smad3. Conclusion: The TGFβ1-smad signaling pathway participates in the IL-33 induced epithelial-to-mesenchymal transition of A549 cells.

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