ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression.
Cancer Lett
; 598: 217118, 2024 Aug 28.
Article
in En
| MEDLINE
| ID: mdl-39002690
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder Neoplasms
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Acyltransferases
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Apoptosis
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Cell Proliferation
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Lipoylation
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Unfolded Protein Response
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Endoplasmic Reticulum Chaperone BiP
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Cancer Lett
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: