scholarly journals EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Hubin Yin ◽  
Chen Zhang ◽  
Zongjie Wei ◽  
Weiyang He ◽  
Ning Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Cell Movement ◽  
Egfr Activation ◽  
Bladder Cancer Cells ◽  
Cancer Tissues ◽  
Multiple Signaling

AbstractBladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.

scholarly journals LINC00958 promotes bladder cancer carcinogenesis by targeting miR-490-3p and AURKA

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hongtao Zhen ◽  
Peng Du ◽  
Qiang Yi ◽  
Xiaolong Tang ◽  
Tongqing Wang
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Method ◽  
Bladder Cancer Cells ◽  
Cell Progression ◽  
New Treatment ◽  
Cancer Tissues ◽  
Proliferation And Invasion

Abstract Background Bladder cancer is a prevalent malignancy of the urinary system, in which long non-coding RNAs (lncRNAs) are highly associated. We aimed to elucidate the role of LINC00958 in bladder cancer. Methods LINC00958 expression levels were measured using qRT-PCR. The interaction of LINC00958-miR-490-3p-AURKA was analyzed by luciferase, RIP, and RNA pull-down assays. The biological roles of LINC00958, miR-490-3p, and AURKA in bladder cancer cells were analyzed using CCK8, BrdU, and transwell assays. Results Increased expression of LINC00958 and AURKA was observed in bladder cancer tissues and cell lines. Decreased LINC00958 expression repressed bladder cancer progression and downregulation of miR-490-3p accelerated bladder cancer cell progression. Moreover, LINC00958 sponges miR-490-3p to upregulate AURKA expression, thereby promoting carcinogenesis in bladder cancer cells. Conclusions Our study revealed that LINC00958 facilitated cell proliferation and invasion, and suppressed cell apoptosis by sponging miR-490-3p and upregulating AURKA, thus inspiring a new treatment method for bladder cancer.

scholarly journals CD82 Suppresses ADAM17-Dependent E-Cadherin Cleavage and Cell Migration in Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhenkun Ma ◽  
Ye Gao ◽  
Wei Liu ◽  
Long Zheng ◽  
Ben Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Progression ◽  
Metalloprotease Activity ◽  
A Disintegrin And Metalloproteinase ◽  
Cancer Tissues ◽  
Inhibitory Regulation ◽  
E Cadherin

CD82 acts as a tumor suppressor in a series of steps in malignant progression. Here, we identified a novel function of CD82 on posttranslational regulating E-cadherin in prostate cancer. In our study, the declined expression of CD82 was verified in prostate cancer tissues and cell lines compared with normal tissue and cell lines. Functionally, CD82 inhibited cell migration and E-cadherin cleavage from the cell membrane in prostate cancer cell. Further study proved that a disintegrin and metalloproteinase ADAM17 as an executor of E-cadherin cleavage mediated the inhibitory regulation of CD82 in E-cadherin shedding in prostate cancer. Specifically, CD82 interacted with ADAM17 and inhibited its metalloprotease activity, which led to the descent of E-cadherin shedding. These results show a nuanced but important role of CD82 in nontranscriptional regulation of E-cadherin, which may help to understand the intricate regulation of dysfunctional adhesion molecule in cancer progression.

scholarly journals EGFR-AS1 Promotes Bladder Cancer Progression by Upregulating EGFR

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Anbang Wang ◽  
Aimin Jiang ◽  
Xinxin Gan ◽  
Zheng Wang ◽  
Jinming Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Diagnostic Marker ◽  
Bladder Cancer Cells ◽  
The Relationship ◽  
Proliferation And Invasion

Long noncoding RNAs play an essential role in bladder cancer progression. The role of long noncoding RNA EGFR-AS1 in bladder cancer needs further study. We used clinical specimens to analyze the relationship between EGFR-AS1 and bladder cancer patients’ characteristics. The functional experiments and mechanism studies were performed using qRT-PCR, transwell assay, survival analysis, and correlation analysis. We found that high expression of EGFR-AS1 was nearly related to aggressive bladder cancer and indicated poor prognosis for patients. The functional experiments in vivo and in vitro suggested that EGFR-AS1 promoted the proliferation and invasion of bladder cancer cells. Mechanically, EGFR-AS1 promoted the expression of EGFR by inhibiting the degradation of EGFR mRNA, thereby promoting the metastasis of bladder cancer. In addition, EGFR-AS1/EGFR may be involved in the immune-related pathways of bladder cancer. These studies indicate that the EGFR-AS1/EGFR pathway may be a potential diagnostic marker and therapeutic target for bladder cancer.

scholarly journals MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/β-Catenin Signaling

2018 ◽  
Vol 48 (2) ◽  
pp. 815-826 ◽  
Author(s):  
Xiaoliang Chen ◽  
Chunshu Jia ◽  
Chunyi Jia ◽  
Xingyi Jin ◽  
Xinquan Gu
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Nuclear Translocation ◽  
Malignant Tumors ◽  
Expression Patterns ◽  
The Cancer Genome Atlas ◽  
Biological Behavior ◽  
Bladder Cancer Cells

Background/Aims: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. Methods: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. Results: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. Conclusion: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

scholarly journals Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway

2018 ◽  
Vol 47 (6) ◽  
pp. 2250-2260 ◽  
Author(s):  
Teng Hou ◽  
Lijie Zhou ◽  
Longwang Wang ◽  
Gallina Kazobinka ◽  
Yumao Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Akt Pathway ◽  
Advanced Tumor Stage ◽  
Large Tumor ◽  
Advanced Tumor ◽  
Bladder Cancer Cells ◽  
The Impact

Background/Aims: Leupaxin (LPXN) is a member of the paxillin protein family. Several studies have reported that LPXN regulates cancer development; however, the role of LPXN in bladder cancer remains unknown. Methods: The expression of LPXN in bladder cancer cells and tissues was determined by real-time PCR, western blotting, and immunohistochemistry, respectively. The biological role of LPXN in bladder cancer cell proliferation, invasion, and angiogenesis was explored both in vitro and in vivo. Results: LPXN expression was elevated in bladder cancer tissues and cell lines compared to adjacent non-tumor tissues and normal urothelial cells. High LPXN expression was correlated with large tumor size, advanced tumor stage, and poor survival in bladder cancer patients. Overexpression of LPXN significantly promoted the proliferation, invasion, and angiogenesis of bladder cancer cells, while suppressing LPXN had the opposite effects. The impact on tumor progression was abolished by inhibiting PI3K/ AKT signaling pathway. We further demonstrated that LPXN probably up-regulated S100P via the PI3K/AKT pathway. Conclusions: LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer.

scholarly journals Androgen activates β-catenin signaling in bladder cancer cells

2013 ◽  
Vol 20 (3) ◽  
pp. 293-304 ◽  
Author(s):  
Yi Li ◽  
Yichun Zheng ◽  
Koji Izumi ◽  
Hitoshi Ishiguro ◽  
Bo Ye ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Strong Association ◽  
Active Form ◽  
Aberrant Expression ◽  
Downstream Target ◽  
Bladder Cancer Cells

Androgen receptor (AR) signals have been implicated in bladder carcinogenesis and tumor progression. Activation of Wnt/β-catenin signaling has also been reported to correlate with bladder cancer progression and poor patients' outcomes. However, cross talk between AR and β-catenin pathways in bladder cancer remains uncharacterized. In radical cystectomy specimens, we immunohistochemically confirmed aberrant expression of β-catenin especially in aggressive tumors. There was a strong association between nuclear expressions of AR and β-catenin in bladder tumors (P=0.0215). Kaplan–Meier and log-rank tests further revealed that reduced membranous β-catenin expression (P=0.0276), nuclear β-catenin expression (P=0.0802), and co-expression of nuclear AR and β-catenin (P=0.0043) correlated with tumor progression after cystectomy. We then assessed the effects of androgen on β-catenin in AR-positive and AR-negative bladder cancer cell lines. A synthetic androgen R1881 increased the expression of an active form of β-catenin and its downstream target c-myc only in AR-positive lines. R1881 also enhanced the activity of β-catenin-mediated transcription, which was abolished by an AR antagonist hydroxyflutamide. Using western blotting and immunofluorescence, R1881 was found to induce nuclear translocation of β-catenin when co-localized with AR. Finally, co-immunoprecipitation revealed androgen-induced associations of AR with β-catenin or T-cell factor (TCF) in bladder cancer cells. Thus, it was likely that androgen was able to activate β-catenin signaling through the AR pathway in bladder cancer cells. Our results also suggest that activation of β-catenin signaling possibly via formation of AR/β-catenin/TCF complex contributes to the progression of bladder cancer, which may enhance the feasibility of androgen deprivation as a potential therapeutic approach.

scholarly journals Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Carrie A. Franzen ◽  
Patricia E. Simms ◽  
Adam F. Van Huis ◽  
Kimberly E. Foreman ◽  
Paul C. Kuo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Internal Standard ◽  
Cancer Recurrence ◽  
High Recurrence Rate ◽  
Bladder Cancer Cells ◽  
Cancer Cell Survival

Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer. Exosomes were isolated by ultracentrifugation from bladder cancer culture conditioned supernatant, labeled with PKH-26, and analyzed on the ImageStreamX with an internal standard added to determine concentration. Exosomes were cocultured with bladder cancer cells and analyzed for internalization. Using the IDEAS software, we determined exosome uptake based on the number of PKH-26+ spots and overall PKH-26 fluorescence intensity. Using unlabeled beads of a known concentration and size, we were able to determine concentrations of exosomes isolated from bladder cancer cells. We measured exosome uptake by recipient bladder cancer cells, and we demonstrated that uptake is dose and time dependent. Finally, we found that uptake is active and specific, which can be partially blocked by heparin treatment. The characterization of cellular uptake and internalization by bladder cancer cells may shed light on the role of exosomes on bladder cancer recurrence and progression.

scholarly journals USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway

2020 ◽  
Author(s):  
Haiqing He ◽  
Bin Zhang ◽  
Bin Yan ◽  
Ming Xiao ◽  
Jiannan Ren ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Annexin V ◽  
Cell Counting ◽  
Cancer Proliferation ◽  
Data Set ◽  
Stat3 Signaling ◽  
Bladder Cancer Cells

Abstract BackgroundBladder cancer is the fourth and tenth most common malignancy in men and women worldwide, respectively. One of the main reasons for the unsatisfactory therapeutic control of bladder cancer is that the molecular biological mechanism of bladder cancer is complex. Gasdermin B (GSDMB) is one member of the gasdermin family and participates in the regulation of cell pyroptosis. The role of GSDMB in bladder cancer has not been studied to date.MethodsThe clinical relevance of GSDMB was examined by the TCGA data set. Functional assays, such as the MTT assay, Celigo fluorescent cell-counting assay, Annexin V-APC assay and xenografts, were used to determine the biological role of GSDMB in bladder cancer. The interaction between GSDMB and STAT3, or GSDMB and USP24 were detected by Mass spectrometry and verified through immunoprecipitation. The relationship between USP24, GSDMB and STAT3 was examined by Western blot analysis and immunohistochemistry.ResultsIn this study, bioinformatics analysis indicated that the mRNA expression level of GSDMB in bladder cancer tissues was higher than that in adjacent normal tissues. Then, we showed that GSDMB promoted bladder cancer progression. Furthermore, we demonstrated that GSDMB interacted with STAT3 to increase the phosphorylation of STAT3 and modulate the glucose metabolism and promote tumor growth in bladder cancer cells. Besides, we also showed that USP24 stabilized GSDMB to activate STAT3 signaling, which was blocked by the USP24 inhibitor. ConclusionsWe suggested that aberrantly up-regulated GSDMB was responsible for enhancing the growth and invasion ability of bladder cancer cells. Then, we showed that GSDMB could bind to STAT3 and activate STAT3 signaling in bladder cancer. Furthermore, we also demonstrated that USP24 interacts with GSDMB and prevents GSDMB from degradation in bladder cancer cells. Therefore, the USP24/GSDMB/STAT3 axis may be a new targetable signaling pathway for bladder cancer treatment.

scholarly journals miR-1-3p Contributes to Cell Proliferation and Invasion by Targeting Glutaminase in Bladder Cancer Cells

2018 ◽  
Vol 51 (2) ◽  
pp. 513-527 ◽  
Author(s):  
Junfeng Zhang ◽  
Longsheng Wang ◽  
Shiyu Mao ◽  
Mengnan Liu ◽  
Wentao Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Methylation Status ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Bladder Cancer Cells ◽  
Cancer Tissues

Background/Aims: Increasing evidence showed that miR-1-3p plays a major role in malignant tumor progression. However, the specific biological function of miR-1-3p in bladder cancer is yet unknown. Methods: The expression levels of miR-1-3p in bladder cancer tissues and cell lines were examined by qRT-PCR. Bisulfite sequencing PCR was used for DNA methylation analysis. The target of miR-1-3p was validated by a dual luciferase reporter assay, and the effects of miR-1-3p on phenotypic changes in bladder cancer cells were investigated in vitro and in vivo. Results: The expression of miR-1-3p in bladder cancer cells was downregulated as compared to normal SV-HUC-1 cells. Also, the expression of miR-1-3p was significantly lower in bladder cancer tissues than the corresponding non-cancerous tissues. The methylation status of CpG islands was involved in the regulation of miR-1-3p expression. miR-1-3p inhibited the bladder cancer cell proliferation, migration, and invasion by directly targeting the 3’-UTR of glutaminase. It also exerted an anti-tumor effect by negatively regulating the glutaminase in a xenograft mouse model. Furthermore, GLS depletion resulted in the prolonged expression of γH2AX. Conclusion: Taken together, these results demonstrated that miR-1-3p acts as a tumor suppressor via regulation of glutaminase expression in bladder cancer progression, and miR-1-3p might represent a novel therapeutic target for the treatment of bladder cancer.

scholarly journals Anti-Cancer Effects and Tumor Marker Role of Glutathione S-Transferase Mu 5 in Human Bladder Cancer

2021 ◽  
Vol 22 (6) ◽  
pp. 3056
Author(s):  
Yeong-Chin Jou ◽  
Shou-Chieh Wang ◽  
Yuan-Chang Dia ◽  
Shou-Tsung Wang ◽  
Min-Hua Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Mitomycin C ◽  
Glutathione S Transferase ◽  
Bladder Cancer Cells ◽  
And Migration ◽  
Cancer Tissues

Our previous study demonstrated that the glutathione S-transferase Mu 5 (GSTM5) gene is highly CpG-methylated in bladder cancer cells and that demethylation by 5-aza-dC activates GSTM5 gene expression. The aim of the present study was to investigate the role of GSTM5 in bladder cancer. The levels of GSTM5 gene expression and DNA methylation were analyzed in patients with bladder cancer, and functional studies of GSTM5 were conducted using GSTM5 overexpression in cultured bladder cancer cells. Clinical analysis revealed that the GSTM5 mRNA expression was lower in bladder cancer tissues than in normal tissues and that the level of GSTM5 DNA methylation was higher in bladder cancer tissues than in normal urine pellets. Overexpression of GSTM5 decreased cell proliferation, migration and colony formation capacity. Glutathione (GSH) assay results indicated that cellular GSH concentration was decreased by GSTM5 expression and that GSH supplementation reversed the decrease in proliferation and migration of cells overexpressing GSTM5. By contrast, a GSH synthesis inhibitor significantly decreased 5637 cell GSH levels, survival and migration. Furthermore, GSTM5 overexpression inhibited the adhesion of cells to the extracellular matrix protein fibronectin. To elucidate the effect of GSTM5 on anticancer drugs used to treat bladder cancer, cellular viability was compared between cells with or without GSTM5 overexpression. GSTM5-overexpressed cells showed no significant change in the cytotoxicity of cisplatin or mitomycin C in 5637, RT4 and BFTC 905 cells. Though a degree of resistance to doxorubicin was noted in 5637 cells overexpressing GSTM5, no such resistance was observed in RT4 and BFTC 905 cells. In summary, GSTM5 plays a tumor suppressor role in bladder cancer cells without significantly affecting chemoresistance to cisplatin and mitomycin C, and the cellular GSH levels highlight a key mechanism underlying the cancer inhibition effect of GSTM5. These findings suggest that low gene expression and high DNA methylation levels of GSTM5 may act as tumor markers for bladder cancer.

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