Chinese medicine Bu-Fei decoction attenuates epithelial-mesenchymal transition of non-small cell lung cancer via inhibition of transforming growth factor β1 signaling pathway in vitro and in vivo

2017 ◽  
Vol 204 ◽  
pp. 45-57 ◽  
Author(s):  
Xi-Ran He ◽  
Shu-Yan Han ◽  
Xiao-Hong Li ◽  
Wen-Xian Zheng ◽  
Li-Na Pang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chinese Medicine ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

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 Role of RUNX2 transcription factor in epithelial mesenchymal transition in non-small cell lung cancer: Epigenetic control of the RUNX2 P1 promoter

Tumor Biology ◽  
2019 ◽  
Vol 41 (5) ◽  
pp. 101042831985101 ◽  
Author(s):  
Angélica María Herreño ◽  
Andrea Carolina Ramírez ◽  
Viviana Paola Chaparro ◽  
María José Fernandez ◽  
Alejandra Cañas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcription Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Lung cancer has a high mortality rate in men and women worldwide. Approximately 15% of diagnosed patients with this type of cancer do not exceed the 5-year survival rate. Unfortunately, diagnosis is established in advanced stages, where other tissues or organs can be affected. In recent years, lineage-specific transcription factors have been associated with a variety of cancers. One such transcription factor possibly regulating cancer is RUNX2, the master gene of early and late osteogenesis. In thyroid and prostate cancer, it has been reported that RUNX2 regulates expression of genes important in tumor cell migration and invasion. In this study, we report on RUNX2/ p57 overexpression in 16 patients with primary non-small cell lung cancer and/or metastatic lung cancer associated with H3K27Ac at P1 gene promoter region. In some patients, H3K4Me3 enrichment was also detected, in addition to WDR5, MLL2, MLL4, and UTX enzyme recruitment, members of the COMPASS-LIKE complex. Moreover, transforming growth factor-β induced RUNX2/ p57 overexpression and specific RUNX2 knockdown supported a role for RUNX2 in epithelial mesenchymal transition, which was demonstrated through loss of function assays in adenocarcinoma A549 lung cancer cell line. Furthermore, RUNX2 increased expression of epithelial mesenchymal transition genes VIMENTIN, TWIST1, and SNAIL1, which reflected increased migratory capacity in lung adenocarcinoma cells.

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