scholarly journals Infiltrating neutrophils increase bladder cancer cell invasion via modulation of androgen receptor (AR)/MMP13 signals

Oncotarget ◽  
2015 ◽  
Vol 6 (40) ◽  
pp. 43081-43089 ◽  
Author(s):  
ChangYi Lin ◽  
WanYing Lin ◽  
Shuyuan Yeh ◽  
Lei Li ◽  
Chawnshang Chang
Keyword(s):  
Bladder Cancer ◽  
Androgen Receptor ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Cancer Cell Invasion

uPAR and mTORC2 as coupled targets for therapeutics development in bladder cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 447-447
Author(s):  
Andrew M. Hau ◽  
Andrew Gilder ◽  
Jing-jing Hu ◽  
Steven L. Gonias ◽  
Donna E. Hansel
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Invasive Bladder Cancer ◽  
Migration And Invasion ◽  
Cancer Cell Invasion ◽  
Cell Migration And Invasion

447 Background: Bladder cancer currently ranks as the fifth most common and the single most expensive cancer to manage in the United States. Although it is established that invasive behavior is a major predictor of diminished outcomes for patients with bladder cancer, the molecular mechanisms governing bladder cancer cell invasion are not well understood. The urokinase receptor (uPAR) and mammalian target of rapamycin complex 2 (mTORC2) represent two powerful pro-invasion candidates that have increased expression in high-grade, invasive bladder cancer, though the former has not been characterized in detail in bladder cancer. Therefore, the aims of this study are to characterize the uPAR signaling network and delineate the signaling interplay between mTORC2 and uPAR in bladder cancer. Methods: Using immunoblot and RT-qPCR analyses, we evaluated uPAR expression in a panel of immortalized bladder cancer cell lines: UROtsa, RT4, UMUC3, T24 and J82. uPAR influence on mTORC1 and mTORC2 signaling was determined by immunoblot analysis following targeted gene-silencing of uPAR using siRNA. Additionally, the effects of uPAR knockdown on cell migration and invasion were investigated using modified scratch-wound migration and transwell invasion assays. Lastly, signaling interplay between uPAR and mTORC2 was investigated by evaluating the effects of uPAR and mTORC2 silencing on Rac1 activity. Results: uPAR knockdown in a subset (T24 and J82) of invasive bladder cancer cell lines inhibited mTORC2, but not mTORC1, activity as measured by P-AKT S473 and P-S6 levels. We found that uPAR silencing in T24 and J82 cells resulted in significant reductions in cell migration and invasion through Matrigel. This is likely attributed to inhibition of Rac1 and decreased lamellipodia formation. Conclusions: Collectively, our results identify uPAR and mTORC2 as major regulators of bladder cancer cell invasion and that these two systems are linked through Rac1. Further investigation of uPAR and mTORC2 inhibition using uPAR-targeting antibodies and mTOR inhibitors in an in vivo mouse model of bladder cancer will determine if these signaling pathways are therapeutically beneficial for the treatment of bladder cancer.

Bladder Cancer Cell Invasion Is Enhanced by Cross-Talk with Fibroblasts Through Hepatocyte Growth Factor

Urology ◽  
2007 ◽  
Vol 69 (4) ◽  
pp. 780-784 ◽  
Author(s):  
Pengfei Wang ◽  
Masa-Aki Nishitani ◽  
Shuji Tanimoto ◽  
Tomoteru Kishimoto ◽  
Tomoharu Fukumori ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cancer Cell ◽  
Cross Talk ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Cancer Cell Invasion ◽  
Hepatocyte Growth

scholarly journals Targeting androgen receptor (AR) with antiandrogen Enzalutamide increases prostate cancer cell invasion yet decreases bladder cancer cell invasion via differentially altering the AR/circRNA-ARC1/miR-125b-2-3p or miR-4736/PPARγ/MMP-9 signals

2021 ◽  
Author(s):  
Gang Deng ◽  
Ronghao Wang ◽  
Yin Sun ◽  
Chi-Ping Huang ◽  
Shuyuan Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bladder Cancer ◽  
Androgen Receptor ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Preclinical Study ◽  
Circular Rnas ◽  
Cancer Cell Invasion

AbstractAndrogen-deprivation therapy (ADT) via targeting androgens/androgen receptor (AR) signals may suppress cell proliferation in both prostate cancer (PCa) and bladder cancer (BCa), yet its impact on the cell invasion of these two urological cancers remains unclear. Here we found targeting androgens/AR with either the recently developed antiandrogen Enzalutamide (Enz) or AR-shRNAs led to increase PCa cell invasion, yet decrease BCa cell invasion. Mechanistic dissection revealed that suppressing androgens/AR signals could result in differential alterations of the selective circular RNAs (circRNAs) as a result of differential endogenous AR transcription. A negative autoregulation in PCa, yet a positive autoregulation in BCa, as a result of differential binding of AR to different androgen-response elements (AREs) and a discriminating histone H3K4 methylation, likely contributes to this outcome between these two urological tumors. Further mechanistic studies indicated that AR-encoded circRNA-ARC1 might sponge/alter the availability of the miRNAs miR-125b-2-3p and/or miR-4736, to impact the metastasis-related PPARγ/MMP-9 signals to alter the PCa vs. BCa cell invasion. The preclinical study using the in vivo mouse model confirms in vitro cell lines data, showing that Enz treatment could increase PCa metastasis, which can be suppressed after suppressing circRNA-ARC1 with sh-circRNA-ARC1. Together, these in vitro/in vivo results demonstrate that antiandrogen therapy with Enz via targeting AR may lead to either increase PCa cell invasion or decrease BCa cell invasion. Targeting these newly identified AR/circRNA-ARC1/miR-125b-2-3p and/or miR-4736/PPARγ/MMP-9 signals may help in the development of new therapies to better suppress the Enz-altered PCa vs. BCa metastasis.

scholarly journals Abstract 3163: Wnt7a promotes bladder cancer cell invasion via canonical Wnt/β-Catenin signaling

2018 ◽  
Author(s):  
Ruimin Huang ◽  
Xiaojing Huang ◽  
Hongwen Zhu ◽  
Junlong Zhuang ◽  
Yu Dong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Cancer Cell Invasion ◽  
Canonical Wnt

ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis

2019 ◽  
Vol 121 (1) ◽  
pp. 231-243
Author(s):  
Ning Xu ◽  
Gen‐Yi Qu ◽  
Yu‐Peng Wu ◽  
Yun‐Zhi Lin ◽  
Dong‐Ning Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Bladder Cancer Cell ◽  
Cancer Cell Invasion ◽  
Node Metastasis
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