Highly stable selenadiazole derivatives induce bladder cancer cell apoptosis and inhibit cell migration and invasion through the activation of ROS-mediated signaling pathways

2016 ◽  
Vol 45 (46) ◽  
pp. 18465-18475 ◽  
Author(s):  
Yahui Yang ◽  
Shulin Deng ◽  
Qinsong Zeng ◽  
Weilie Hu ◽  
Tianfeng Chen
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Bladder Cancer Cell ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Cancer Cell Apoptosis

Herein highly stable selenadiazole derivatives were synthesized and found to be able to induce bladder cancer cell apoptosis and inhibit cell migration and invasion through the activation of ROS-mediated pathways.

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.

scholarly journals miR-451 suppresses bladder cancer cell migration and invasion via directly targeting c-Myc

2016 ◽  
Vol 36 (4) ◽  
pp. 2049-2058 ◽  
Author(s):  
Jun Wang ◽  
Xiaomei Zhao ◽  
Jianhua Shi ◽  
Yiwei Pan ◽  
Qinghai Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Bladder Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion
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