scholarly journals Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF-β Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ninggang Yang ◽  
Jing Gao ◽  
Ruizhen Hou ◽  
Xiaoli Xu ◽  
Ningqiang Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Grape Seed ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Grape Seed Proanthocyanidins ◽  
Bladder Cancer Cells ◽  
Underlying Mechanisms

Bladder cancer (BC) is the most common cancer of the urinary system. Despite advances in diagnosis and therapy, the prognosis is still poor because of recurrence and metastasis. Epithelial-mesenchymal transition (EMT) is considered to play an important role in the invasion and metastasis of BC. Grape seed proanthocyanidins (GSPs) exhibit chemopreventive and chemotherapeutic activities against several types of cancer. However, their effects and underlying mechanisms on the invasive potential of BC remain unclear. In this study, we found that GSPs inhibited migration, invasion, and MMP-2/-9 secretion of both T24 and 5637 bladder cancer cells at noncytotoxic concentrations. We also discovered that 5637 cells were more suitable than T24 cells for the EMT study. Further study showed that GSPs inhibited EMT by reversing the TGF-β-induced morphological change and upregulation of mesenchymal markers N-cadherin, vimentin, and Slug as well as downregulation of epithelial markers E-cadherin and ZO-1 in 5637 cells. GSPs also inhibited TGF-β-induced phosphorylation of Smad2/3, Akt, Erk, and p38 in 5637 cells without affecting the expression of total Smad2/3, Akt, Erk, and p38. Taken together, the results of the present study demonstrate that GSPs effectively inhibit the migration and invasion of BC cells by reversing EMT through suppression of the TGF-β signaling pathway, which indicates that GSPs could be developed as a potential chemopreventive and therapeutic agent against bladder cancer.

scholarly journals Aloperine prevents hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells through regulating the mTOR/p70S6K/4E-BP1 pathway

2020 ◽  
Author(s):  
Weiling Lv ◽  
Qian Liu ◽  
Jihong An ◽  
Xiaoyong Song
Keyword(s):  
Bladder Cancer ◽  
Western Blot ◽  
Cell Viability ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Protein Levels ◽  
T24 Cells ◽  
Bladder Cancer Cells

Abstract Background: Aloperine (ALO), a novel active alkaloid extracted from S. alopecuroide, has been reported to possess anti-tumor effect. However, its potential effect on bladder cancer remains unknown. Therefore, the objective of this study was to investigate the effect of ALO bladder cancer cells under hypoxia condition.Methods: Human bladder cancer cell line T24 cells were treated with different concentrations of ALO and maintained in hypoxic condition for 12, 24, or 48 h. MTT assay was performed to detect cell viability. Transwell assay was performed to detect cell migration and invasion. Epithelial-mesenchymal transition (EMT) was evaluated by detecting the expression levels of E-cadherin, N-cadherin, and vimentin using western blot. The mRNA and protein levels of HIF-1α, snail, slug, and twist1 were measured using qRT-PCR and western blot. The expression levels of mTOR/p70S6K/4E-BP1 pathway-related proteins were detected using western blot.Results: Our results showed that ALO inhibited the cell viability of T24 cells cultured in hypoxia condition. ALO also attenuated hypoxia-induced migration and invasion of T24 cells. We also found that ALO treatment caused a significant increase in E-cadherin expression and decreases in N-cadherin and vimentin expressions. Besides, ALO dose-dependently inhibited the expressions of EMT inducers including snail, slug, and twist1 both in mRNA and protein levels in T24 cells induced by hypoxia. Furthermore, ALO significantly inhibited HIF-1α protein synthesis and phosphorylation of mTOR, as well 4E-BP1 and p70S6K in hypoxia-induced T24 cells.Conclusion: These results indicated that ALO exerted anti-tumor effect on bladder cancer in vitro via inhibiting the activation of mTOR/p70S6K/4E-BP1 pathway.

scholarly journals Exosome-Derived LINC00960 and LINC02470 Promote the Epithelial-Mesenchymal Transition and Aggressiveness of Bladder Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1419
Author(s):  
Cheng-Shuo Huang ◽  
Jar-Yi Ho ◽  
Jung-Hwa Chiang ◽  
Cheng-Ping Yu ◽  
Dah-Shyong Yu
Keyword(s):  
Bladder Cancer ◽  
Notch Signaling ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Exosomes are essential for several tumor progression-related processes, including the epithelial–mesenchymal transition (EMT). Long non-coding RNAs (lncRNAs) comprise a major group of exosomal components and regulate the neoplastic development of several cancer types; however, the progressive role of exosomal lncRNAs in bladder cancer have rarely been addressed. In this study, we identified two potential aggressiveness-promoting exosomal lncRNAs, LINC00960 and LINC02470. Exosomes derived from high-grade bladder cancer cells enhanced the viability, migration, invasion and clonogenicity of recipient low-grade bladder cancer cells and activated major EMT-upstream signaling pathways, including β-catenin signaling, Notch signaling, and Smad2/3 signaling pathways. Nevertheless, LINC00960 and LINC02470 were expressed at significantly higher levels in T24 and J82 cells and their secreted exosomes than in TSGH-8301 cells. Moreover, exosomes derived from LINC00960 knockdown or LINC02470 knockdown T24 cells significantly attenuated the ability of exosomes to promote cell aggressiveness and activate EMT-related signaling pathways in recipient TSGH-8301 cells. Our findings indicate that exosome-derived LINC00960 and LINC02470 from high-grade bladder cancer cells promote the malignant behaviors of recipient low-grade bladder cancer cells and induce EMT by upregulating β-catenin signaling, Notch signaling, and Smad2/3 signaling. Both lncRNAs may serve as potential liquid biomarkers for the prognostic surveillance of bladder cancer progression.

SENP2 suppresses epithelial-mesenchymal transition of bladder cancer cells through deSUMOylation of TGF-βRI

2017 ◽  
Vol 56 (10) ◽  
pp. 2332-2341 ◽  
Author(s):  
Mingyue Tan ◽  
Dingguo Zhang ◽  
Encheng Zhang ◽  
Dongliang Xu ◽  
Zhihong Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

scholarly journals Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial–Mesenchymal Transition

2021 ◽  
Vol 9 ◽  
Author(s):  
Jun Zou ◽  
Ruiyan Huang ◽  
Yanfei Chen ◽  
Xiaoping Huang ◽  
Huajun Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Pyruvate Kinase ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Aerobic Glycolysis ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells ◽  
Malignant Behavior

BackgroundAerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression.MethodsThe expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells.FindingsThe results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial–mesenchymal transition in bladder cancer cells.InterpretationIn conclusion, the results suggest that DPYSL2 promotes aerobic glycolysis and EMT in bladder cancer via PKM2, serving as a potential therapeutic target for bladder cancer treatment.

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