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Experts Show That YAP1/mTOR Interaction Accelerates Bladder Cancer Progression
Study results suggest that the interaction between yes-associated protein 1 (YAP1) and mammalian target of rapamycin (mTOR) hastens disease progression in patients with bladder cancer (Int J Oncol. 2019 Nov 25. Epub ahead of print).
“[YAP1 and mTOR]…signaling pathways have been found to be deregulated in bladder cancer and accelerate the malignant progression of bladder cancer,” explained Mingxi Xu, MD, Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , The People’s Republic of China, and colleagues.
“However, the crosstalk between YAP1 and mTOR and its role in bladder cancer progression remains unclear,” they continued. Because of this, Dr Xu et al conducted a study to evaluate the crosstalk between mTOR and YAP1.
Compared with adjacent normal tissues, bladder cancer tissues had elevated expression of YAP1 and mTOR. When mTOR or YAP1 were knocked down with siRNA transfection, the proliferation ability and induced apoptosis of HT-1376 and J82 bladder cancer cells was stifled significantly, especially in cases where YAP1 and mTOR were downregulated concurrently.
In situations of mTOR upregulation, the mRNA and protein levels of YAP1 were increased, as was its nuclear accrual, and when YAP1 was upregulatied, mTOR expression and stability was increased and its protein degradation was reduced.
“In addition, immunofluorescence and Duolink assays demonstrated that YAP1 and mTOR were co-localized in the nucleus. Immunoprecipitation assay demonstrated that the YAP1 protein was able to bind to the mTOR protein,” Dr Xu and co-investigators added.
Of note, YAP1 was observed to combine with S-phase kinase-associated protein 2 (SKP2) which led to the positive regulation of its expression. When SKP2 was downregulated in HT-1376 and J82 cells, it ended cell growth and cell apoptosis inhibition induced by YAP1 overexpression.
“Taken together, the findings of the present study indicated that the crosstalk between YAP1 and mTOR plays a pivotal role in accelerating the progression of bladder cancer, which may provide new insights into the role of the YAP1/mTOR axis in the occurrence and development of bladder cancer,” Dr Xu and colleagues concluded.—Hina Porcelli
