scholarly journals FOXO1 Inhibits Tumor Cell Migration via Regulating Cell Surface Morphology in Non-Small Cell Lung Cancer Cells

2018 ◽  
Vol 48 (1) ◽  
pp. 138-148 ◽  
Author(s):  
Zhuo Gao ◽  
Ruiqi Liu ◽  
Na Ye ◽  
Chao Liu ◽  
Xiuli Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Surface ◽  
Human Lung ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Cell Surface Morphology

Background/Aims: Cell surface morphology plays pivotal roles in malignant progression and epithelial-mesenchymal transition (EMT). Previous research demonstrated that microvilli play a key role in cell migration of non-small cell lung cancer (NSCLC). In this study, we report that Forkhead box class O1 (FOXO1) is downregulated in human NSCLC and that silencing of FOXO1 is associated with the invasive stage of tumor progression. Methods: The cell proliferation, migration, and invasion were characterized in vitro, and we tested the expression of the Epithelial-mesenchymal transition (EMT) marker by immunofluorescence staining and also identified the effect of FOXO1 on the microvilli by scanning electron microscopy (SEM). Results: Functional analyses revealed that silencing of FOXO1 resulted in an increase in NSCLC cell proliferation, migration, and invasion; whereas overexpression of FOXO1 significantly inhibited the migration and invasive capability of NSCLC cells in vitro. Furthermore, cell morphology imaging showed that FOXO1 maintained the characteristics of epithelial cells. Immunofluorescence staining and western blotting showed that the E-cadherin level was elevated and Vimentin was reduced by FOXO1 overexpression. Conversely, the E-cadherin level was reduced and Vimentin was elevated in cells silenced for FOXO1. Furthermore, scanning electron microscopy (SEM) showed that FOXO1 overexpression increased the length of the microvilli on the cell surface, whereas FOXO1 silencing significantly reduced their length. Conclusions: FOXO1 is involved in human lung carcinogenesis and may serve as a potential therapeutic target in the migration of human lung cancer.

Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

2019 ◽  
Author(s):  
Zongli Ding ◽  
Wenwen Du ◽  
Zhe Lei ◽  
Yang Zhang ◽  
Jianjie Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wound Healing ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Wound Healing Assay ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background: TGF-β1 signaling is a potent inducer of epithelial-mesenchymal transition (EMT) in various cancers. Our previous study has indicated that NRP1 was significantly up-regulated and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the function of NRP1 in regulation of TGF-β1-induced EMT and NSCLC cell migration and invasion remained unclear. Methods: The differential expression level of NRP1 was determined by RT-PCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine cell ability of migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanism. Results: Increased expression of NRP1 was found in metastatic NSCLC tissues and can promote NSCLC metastasis in vivo. Transwell assays, wound healing assay and western blot analysis showed that knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of A549 and H226 cells. Furthermore, overexpression of NRP1 could weak the decreased migratory and invasive capabilities with SIS3 treatment. Co-IP data showed that NRP1 can interact with TGFβRⅡ to induce EMT. Conclusion: This is the first time to report that NRP1 can modulate TGF-β1-induced EMT and cell migration and invasion in NSCLC.

scholarly journals Triptolide suppresses the growth and metastasis of non-small cell lung cancer by inhibiting β-catenin-mediated epithelial–mesenchymal transition

2021 ◽  
Author(s):  
Qiu-di Deng ◽  
Xue-ping Lei ◽  
Yi-hang Zhong ◽  
Min-shan Chen ◽  
Yuan-yu Ke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Small Cell ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

AbstractNon-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

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