ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression
View abstract on PubMed
Summary
This summary is machine-generated.ZDHHC9, a newly identified oncogene, drives bladder cancer (BCa) progression and drug resistance by inhibiting the unfolded protein response. Targeting ZDHHC9 may offer a new therapeutic strategy for BCa treatment.
Area Of Science
- Oncology
- Molecular Biology
- Biochemistry
Background
- Palmitoylation is a post-translational modification crucial in signaling pathways implicated in tumorigenesis and drug resistance.
- The specific role of palmitoylation in bladder cancer (BCa) development is not well understood.
- ZDHHC9 is identified as a significantly upregulated oncogene in BCa.
Purpose Of The Study
- To investigate the role of ZDHHC9 in bladder cancer (BCa) development and its potential as a therapeutic target.
- To elucidate the molecular mechanism by which ZDHHC9 influences BCa progression and drug resistance.
Main Methods
- Gene expression analysis to identify upregulated oncogenes in BCa.
- ZDHHC9 knockdown experiments to assess functional impact on tumor proliferation, apoptosis, and drug sensitivity.
- Mechanism studies involving SP1, ZDHHC9, Bip protein, and unfolded protein response (UPR) pathways.
- Analysis of protein stability and cellular localization.
Main Results
- ZDHHC9 was significantly upregulated in BCa and acted as an oncogene.
- Knockdown of ZDHHC9 inhibited tumor proliferation, induced apoptosis, and enhanced gemcitabine (GEM) and cisplatin (CDDP) efficacy.
- SP1 transcriptionally activated ZDHHC9 expression.
- ZDHHC9 palmitoylated Bip protein at Cys420, inhibiting the unfolded protein response (UPR), enhancing Bip stability, and preserving ER localization.
Conclusions
- ZDHHC9 plays a critical role in bladder cancer progression and chemoresistance.
- ZDHHC9-mediated palmitoylation of Bip inhibits the UPR, contributing to oncogenesis.
- ZDHHC9 represents a potential novel therapeutic target for BCa.
- ZDHHC9 inhibition could enhance the efficacy of combination therapy with GEM and CDDP.
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