scholarly journals Downregulation of FOXP2 promotes breast cancer migration and invasion through TGFβ/SMAD signaling pathway

2018 ◽  
Author(s):  
Meng‑Ting Chen ◽  
He‑Fen Sun ◽  
Liang‑Dong Li ◽  
Yang Zhao ◽  
Li‑Peng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
Smad Signaling ◽  
Cancer Migration ◽  
Smad Signaling Pathway

scholarly journals LncRNA NEAT1 promotes proliferation, migration, invasion and epithelial-mesenchymal transition process in TGF-β2-stimulated lens epithelial cells through regulating the miR-486-5p/SMAD4 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Huajun Wang ◽  
Guangying Zheng
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathway ◽  
Luciferase Reporter ◽  
Posterior Capsular Opacification ◽  
Lens Epithelial Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Mesenchymal Transformation

Abstract Background Abnormal proliferation, metastasis and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are direct factors of posterior capsular opacification (PCO). Nuclear enriched abundant transcript 1 (NEAT1) has been shown to promote cell proliferation, metastasis and EMT, but whether it affects the progression of PCO is unclear. Methods The expression of NEAT1, microRNA-486-5p (miR-486-5p) and Drosophila mothers against decapentaplegic 4 (SMAD4) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of cells was measured via 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was employed to detect the migration and invasion of cells. The levels of EMT marker proteins, SMAD4 protein and transforming growth factor-β (TGF-β)/SMAD signaling pathway-related proteins were assessed by western blot (WB) analysis. Further, the relationship between miR-486-5p and NEAT1 or SMAD4 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and biotin-labeled RNA pull-down assay. Results NEAT1 is upregulated and miR-486-5p is downregulated in the posterior capsular tissues of PCO patients and TGF-β2-induced LECs. Interference of NEAT1 reverses the promoting effect of TGF-β2 on the proliferation, migration, invasion and EMT of LECs. MiR-486-5p can be sponged by NEAT1, and its inhibitor reverses the suppression effect of NEAT1 silencing on the progression of TGF-β2-induced LECs. SMAD4 functions as a target of miR-486-5p, and its overexpression recovers the inhibition effect of miR-486-5p overexpression on the progression of TGF-β2-induced LECs. The activity of the TGF-β/SMAD signaling pathway is regulated by the NEAT1/miR-486-5p/SMAD4 axis. Conclusion Our study shows that NEAT1 has a positive effect on the progression of PCO and is expected to become a new target for PCO treatment.

Abstract 187: Epigenetic memory during breast cancer progression is sustained by Smad signaling pathway

2010 ◽  
Author(s):  
Sam Thiagalingam ◽  
Arthur W. Lambert ◽  
Sait Ozturk ◽  
Hamid M. Abdolmaleky ◽  
Panagiotis Papageorgis
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Epigenetic Memory ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals Integrative analysis of the canonical TGF?-Smad signaling pathway in breast cancer (Preprint)

2017 ◽  
Author(s):  
Dan Zhou ◽  
Weiwei Tang ◽  
Yun Zhang ◽  
Hanxiang An
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Luminal A ◽  
Independent Manner ◽  
Free Survival ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Cancer Pathogenesis ◽  
Smad Signaling Pathway

BACKGROUND Breast cancer deaths are mainly attributed to metastasis, while epithelial to mesenchymal transition (EMT) plays a pivotal role in promoting cancer cell metastasis. EMT is activated by various stimuli, resulting in different therapeutic responses. The TGFβ signaling pathway is a canonical driver of EMT, and many molecular drugs are developed to target this pathway. However, the alternations of this pathway in BC remain elusive. OBJECTIVE The aim of this study was to investigate the relationship between the canonical TGFβ-Smad signaling pathway and breast cancer pathogenesis. METHODS Herein, we investigated the mutational, transcriptional, epigenetic and post-transcriptional alternations of 14 core members in this pathway through bioinformatics approach by analyses of 56,496 BC patients from various public databases, including COSMIC, Oncomine, DiseaseMeth and Starbase. A protein-protein interaction network was derived from Cytoscape software. Associations of these selected members with relapse free survival (RFS), overall survival (OS), distant metastases free survival (DMFS) and post progression survival (PPS) were performed using the Kaplan-Meier plotter online tool. RESULTS Our integrated analyses revealed that Smad4 was the most frequently mutated member of the TGFβ-Smad pathway in BC with a mutation frequency of 0.85% (30/3537). The expression levels of TGFβ1, TGFβ3, Smad1, Smad2 and Smad7 were significantly higher, whereas TGFβ2, ALK1, ALK2, ALK5, TGFβR2, Smad3, Smad4, Smad5 and Smad6 were downregulated in BC compared with normal subjects (P<0.001). Evaluation of epigenetic alteration identified that the promoters of ALK1 (P=0.000e+00), ALK2 (P=2.22e-16) and ALK5 (P=1.625e-12) were hypermethylated in 1,274 BC samples. In contrast, Smad2 (P=6.56e-04) was significantly hypomethylated in BC. Although all 14 members had potential diagnostic significances with different prediction power (AUC ranging from 0.788 to 1.00) in various subtypes of BC, only TGFβ3 could predict RFS (HR=0.69, 95% CI [0.62-0.77]), OS (HR=0.69, 95% CI [0.56-0.86]), DMFS (HR=0.8, 95% CI [0.66-0.97]) and PPS (HR=0.76, 95% CI [0.6-0.97]) for patients with BC in an independent manner. Additionally, 11 out of 14 members were associated with RFS in luminal A BC. CONCLUSIONS Our results indicated that TGFβ-Smad pathway core members could serve as novel diagnostic and prognostic biomarkers in BC.

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 Bleomycin Suppresses the Proliferation and the Mobility of Human Gastric Cancer Cells Through the Smad Signaling Pathway

2016 ◽  
Vol 40 (6) ◽  
pp. 1401-1409 ◽  
Author(s):  
Jin-fang Liu ◽  
Xiao-cui Nie ◽  
You-cheng Shao ◽  
Wen-hui Su ◽  
Hai-ying Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Annexin V ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Background/Aims: Extensive studies have demonstrated that Bleomycin (BLM) is a glycopeptide antibiotic that has been used as an anticancer chemotherapeutic reagent. It can induce both single- and double-strand DNA damage, inhibit synthesis of DNA, suppress proliferation, and induce apoptosis in cancer cells. Smad signaling transducers are considered as important molecules in tumor development and progression, and may closely be related to the biological behaviors of some malignant carcinomas, including gastric cancer. Methods: The effects of different concentrations of BLM on the proliferation, cell cycle, apoptosis, migration, and invasion on gastric cancer cell lines MKN45 and AGS were assayed by using CCK-8 assay, Annexin V/PI double staining, PI staining, and transwell assay. Western blot and Immunohistochemistry were applied to analyze the potential mechanism(s). Results: BLM treatment resulted in a low proliferation, high apoptosis, low migration and invasion in MKN45 and AGS cells. Furthermore, the possible mechanisms underlying that Smad3 activity could be changed after binding with BLM, and subsequently the Smad signaling pathway had a cascade response. Conclusion: These results highlight BLM as an exciting theme for gastric cancer treatment, which may represent an effective clinical therapeutic reagent for gastric cancer patients.

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