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Evaluation of the Efficacy of the H. pylori Protein HP-NAP as a Therapeutic Tool for Treatment of Bladder Cancer in an Orthotopic Murine Model
Published on: May 29, 2015
ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression
Weiquan Li1, Jingchong Liu1, Tiexi Yu1
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen, 518000, China.
Abstract:
Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.
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