Cisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1/2-AP-1 signaling pathway
Authors: Hung-En Chen
Thomas I-Sheng Hwang
Chao-Yen Ho
Te-Fu Tsai
Yi-Chia Lin
Po-Chun Chen
Ji-Fan Lin
Kuang-Yu Chou
Journal: Bioscience reports (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Bladder cancer; ERK; PD-L1; cisplatin.
Affiliations: Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan., Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan., Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan., Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan., Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan  ., Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan., Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan., Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan  ., Department of Urology, Taipei Medical University, Taipei, Taiwan.

Abstract:  Bladder cancer (BC) is the second most common urologic malignancy and the ninth most common malignancy worldwide. Surgical resection is the mainstay of treatment for patients with early-stage disease, whereas therapeutic options are limited for patients with advanced-stage or residual BC. Programmed cell death ligand-1 (PD-L1) is an important target for immunotherapy. It is known that PD-L1 is overexpressed in BC; a clinical trial involving PD-L1 immune checkpoint inhibitors in advanced BC is ongoing. In the present study, we used Western blot and quantitative real-time PCR (qPCR) to define the expression level of PD-L1 after cisplatin treatment in BC-derived cell lines. The signal activation was also evaluated by Western blot in BC-derived cell lines. We found that chemotherapeutic drug cisplatin can induce PD-L1 but not PD-L2 expression in BC-derived cell lines. Furthermore, the expression level of PD-L1 was increased in a dose- and time-dependent manner after cisplatin treatment. The cisplatin-induced PD-L1 expression is mainly mediated by ERK1/2 but not Akt/mTOR signal pathway. Moreover, we found that cisplatin activates transcription factor activator protein-1 (AP-1) to regulate PD-L1 expression. The chemotherapy drug such as cisplatin may trigger resistance of BC through PD-L1 up-regulation. The present study suggests that PD-L1 antibody should be used concomitantly with chemotherapy in the setting of advanced and metastatic BC. 

Retracted: No

PubPeer comments:
 Figure 6A and 6C appear to include a repeated band. Could the authors please review and provide an original uncropped scan? *** ![file] , 
 https: doi.org 10.1042 BSR-20190362_COR The authors of the original article u201cCisplatin contributes to programmed death-ligand 1 expression in bladder cancer through ERK1 2-AP-1 signaling pathwayu201d (Biosci Rep (2019) 39(9), DOI: 10.1042 BSR20190362) would like to correct errors in their figures. The Western blot images for Figure 6A (p-c-Jun) and 6C (p-c-Jun), as well as Figure 3A (p-mTOR; the 3rd blot from top) and Figure 3B (the 2nd blot from top; Akt) were mistakenly repeated. **Figure 3** ![file] In their experiment, all results were repeated in more than three independent runs. Due to lack of experience with handling a substantial quantity of Western blot data, mistakes had occurred during the arrangement of the final Figures 3 and 6. **Figure 6** ![file] The corrected Figures 3 and 6 are presented in this article. The authors sincerely apologise for this mistake and wish to amend their error. The results and conclusion of their study remain the same. ,