Notch-3 promote angiogenesis and proliferation of bladder cancer cells through the PI3K/Akt pathway

2016 ◽  
Vol 4 (3) ◽  
pp. 314-328
Author(s):  
Joan V. Draucker ◽  
Irene Talarico
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Transitional Cell ◽  
Frozen Storage ◽  
Benign Prostatic Hypertrophy ◽  
Akt Pathway ◽  
Bladder Cancer Patient ◽  
Notch 3 ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

Transitional cell carcinoma (TCC) of the bladder is the most common form of bladder cancer and is manifested in two distinct forms with different clinical and biological behaviors. Approximately 70% of patients present with non-muscle invasive tumors, while the remaining 30% present with muscle-invasive tumors. Despite good prognosis for patients with superficial disease, recurrence is common and is associated with development of muscle-invasive disease. Seventy seven tissue specimens from bladder cancer patient [32- noninvasive and 45- muscle invasive] and forty specimens from patients with benign prostatic hypertrophy as control were enrolled. The specimen’s tissue was halved into either in 10% neutral buffered formalin for histological process or snap frozen storage in liquid nitrogen. Tissue RNA and protein were examined by qPCR and western blot for Noch-3 and PI3K/Akt pathway respectively. One-Way ANOVA with Bonferroni tests was applied, with significance accepted at P<0.05. Our results highlight critical, overlooked functions for Notch-3 in regulating angiogenesis and proliferation of bladder cancer cells and suggest that Notch-3 inhibitor may be drug target in bladder cancer. Further investigation into the precise mechanism for this protection is warranted.

Role of heat shock protein 90 inhibition with 17-(allylamino)-17 (demethoxygeldenamycin) in muscle-invasive bladder cancer cells.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 273-273
Author(s):  
H. Williams
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Heat Shock Protein 90 ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

273 Background: Muscle invasive bladder cancer portends a poor long term prognosis. Platinum based therapy is the mainstay of treatment but more effective agents are needed for management of this disease. Heat shock protein 90 (Hsp90) is a ubiquitous protein that has been shown to be overexpressed in tumor cells. It functions as a molecular chaperone responsible for the stability and function of a number of proteins critical to the oncogenic process. 17-(allylamino)-17 demethoxygeldanamycin (17 AAG) is a Hsp90 inhibitor that is currently in phase III trials in several tumor models. The purpose of this study was to evaluate the role of 17 AAG treatment for bladder cancer in vitro. Methods: Seven bladder cancer cell lines representing muscle invasive bladder cancer were treated in the presence and absence of 17 AAG. Both short term and long term treatments were evaluated for their effects on growth, motility and invasion of the cancer cells. Expression of proteins involved in cell growth, survival and metastasis were evaluated with Western blotting. Results: Our data demonstrated that 17 AAG treatment resulted in induction of apoptosis, inhibition of cell cycle progression through inhibition of MAP kinase pathway and cyclin D1 expression. Decreased tumor cell motility and invasion was observed with 17 AAG treatment. Several intracellular signaling pathways involved in cell proliferation, invasion and metastasis were inhibited. Conclusions: Hsp90 inhibition in muscle invasive bladder cancer cells impacts growth, motility and invasiveness by inhibiting numerous intracellular signaling pathways. Taken together, these findings suggest a possible role for Hsp90 inhibitors in bladder cancer tumorigenesis. No significant financial relationships to disclose.

scholarly journals COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway in human bladder cancer cells

2005 ◽  
Vol 37 (3) ◽  
pp. 199-203 ◽  
Author(s):  
Eun-Mi Choi ◽  
Sahng-June Kwak ◽  
Young-Myeong Kim ◽  
Kwon-Soo Ha ◽  
Jong-Il Kim ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Akt Pathway ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Cox 2 ◽  
Human Bladder Cancer Cells

scholarly journals Nanaomycin K inhibited epithelial mesenchymal transition and tumor growth in bladder cancer cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koichi Kitagawa ◽  
Katsumi Shigemura ◽  
Aya Ishii ◽  
Takuji Nakashima ◽  
Hirotaka Matsuo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Bladder Cancer Cells ◽  
And Migration ◽  
Muscle Invasive

AbstractNanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966T, has been discovered to have inhibitory bioactivity on epithelial–mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression. We treated two bladder cancer lines, non-muscle-invasive KK47 and muscle-invasive T24, with nanaomycin K to determine the effects on cell proliferation, apoptosis and expression of EMT markers in vitro. Wound-healing assays were performed to assess cell invasion and migration. We conducted an in vivo xenograft study in which mice were inoculated with bladder cancer cells and treated with intratumoral administration of nanaomycin K to investigate its anti-tumor and EMT inhibition effects. As the results, nanaomycin K (50 µg/mL) significantly inhibited cell proliferation in KK47 (p < 0.01) and T24 (p < 0.01) in the presence of TGF-β, which is an EMT-inducer. Nanaomycin K (50 µg/mL) also significantly inhibited cell migration in KK47 (p < 0.01) and T24 (p < 0.01), and induced apoptosis in both cell lines in the presence of TGF-β (p < 0.01). Nanaomycin K increased the expression of E-cadherin and inhibited the expression of N-cadherin and vimentin in both cell lines. Nanaomycin K also decreased expression of Snail, Slug, phospho-p38 and phospho-SAPK/JNK especially in T24. Intratumoral administration of nanaomycin K significantly inhibited tumor growth in both KK47 and T24 cells at high dose (1.0 mg/body) (p = 0.009 and p = 0.003, respectively) with no obvious adverse events. In addition, nanaomycin K reversed EMT and significantly inhibited the expression of Ki-67 especially in T24. In conclusion, we demonstrated that nanaomycin K had significant anti-EMT and anti-tumor effects in bladder cancer cells, suggesting that nanaomycin K may be a therapeutic candidate for bladder cancer treatment.

scholarly journals Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression

2021 ◽  
Vol 22 (23) ◽  
pp. 12756
Author(s):  
Xuan-Mei Piao ◽  
Chaelin You ◽  
Young Joon Byun ◽  
Ho Won Kang ◽  
Junho Noh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Mitotic Checkpoint ◽  
Invasive Bladder Cancer ◽  
Common Disease ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive ◽  
Normal Controls

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

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 SLC35F2, a Transporter Sporadically Mutated in the Untranslated Region, Promotes Growth, Migration, and Invasion of Bladder Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 80
Author(s):  
Roland Kotolloshi ◽  
Martin Hölzer ◽  
Mieczyslaw Gajda ◽  
Marc-Oliver Grimm ◽  
Daniel Steinbach
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Untranslated Region ◽  
Tumour Cells ◽  
Invasive Bladder Cancer ◽  
Migration And Invasion ◽  
Sequencing Analysis ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Cancer Cells ◽  
Muscle Invasive

Bladder cancer is a very heterogeneous disease and the molecular mechanisms of carcinogenesis and progression are insufficiently investigated. From the DNA sequencing analysis of matched non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) samples from eight patients, we identified the tumour-associated gene SLC35F2 to be mutated in the 5′ and 3′ untranslated region (UTR). One mutation in 3′UTR increased the luciferase activity reporter, suggesting its influence on the protein expression of SLC35F2. The mRNA level of SLC35F2 was increased in MIBC compared with NMIBC. Furthermore, in immunohistochemical staining, we observed a strong intensity of SLC35F2 in single tumour cells and in the border cells of solid tumour areas with an atypical accumulation around the nucleus, especially in the MIBC. This suggests that SLC35F2 might be highly expressed in aggressive and invasive tumour cells. Moreover, knockdown of SLC35F2 repressed the growth of bladder cancer cells in the monolayer and spheroid model and suppressed migration and invasion of bladder cancer cells. In conclusion, we suggest that SLC35F2 is involved in bladder cancer progression and might provide a new therapeutic approach, for example, by the anti-cancer drug YM155, a cargo of the SLC35F2 transporter.

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