Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues
SCIE
SCOPUS
- Title
- Targeting XBP1-mediated β-catenin expression associated with bladder cancer with newly synthetic Oridonin analogues
- Authors
- YUN, EUN JIN; Chen, Wei; Zhou, Jiancheng; Wu, Kaijie; Huang, Jun; Ding, Ye; Wang, Bin; Ding, Chunyong; Hernandez, Elizabeth; Santoyo, John; Chen, Haiying; Lin, Ho; Sagalowsky, Arthur; He, Dalin; Zhou, Jia; Hsieh, Jer-Tsong
- Date Issued
- 2016-08-30
- Publisher
- IMPACT JOURNALS LLC
- Abstract
- Conventional chemotherapy is commonly used for advanced stages of transitional cell carcinoma (TCC) with modest success and high morbidity; however, TCC eventually develops resistance. Muscle invasive bladder cancer (MIBC) is recognized as a lethal disease due to its poor response to traditional chemotherapy. Numerous studies have implicated beta-catenin, a critical effector in Wnt-mediated pathway associated with epithelial-mesenchymal transition and cancer stem cell, is involved in TCC progression, and furthermore closely associated with chemo-resistance. In this study, we discovered a novel natural product analogue CYD 6-17 that has a potent inhibitory effect on TCC cells exhibiting drug resistance to various chemotherapeutics, with an IC50 at nM range. Delivery of CYD 6-17 significantly inhibited the tumor growth using xenograft model but without detectable side effects. Mechanistically, it targeted beta-catenin gene transcription by decreasing the binding of XBP1 to the promoter region, which appeared to be a new regulatory mechanism for beta-catenin gene expression. Clinically, XBP1 expression correlated with the poor overall survival of patients. Overall, this study unveils unique mechanism of beta-catenin gene regulation in advanced TCC and also offers a potential rational therapeutic regimen to MIBC.
- Keywords
- UROTHELIAL CARCINOMAS; SIGNALING PATHWAY; IN-VITRO; CHEMORESISTANCE; WNT; ACTIVATION; PROTEIN; CELLS; GENE; THERAPY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/39244
- DOI
- 10.18632/oncotarget.10863
- ISSN
- 1949-2553
- Article Type
- Article
- Citation
- Oncotarget, vol. 7, no. 35, page. 56842 - 56854, 2016-08-30
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- There are no files associated with this item.
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