ArticleNPJ precision oncology2026
ASF1B promotes gastric cancer liver metastasis through inhibiting ZDHHC9/PCBP1/ SLC7A11 signaling axis mediated ferroptosis.
Article in NPJ precision oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The trial behind it
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Who cites it
4 citing papers in PubMed.
- Experimental Detection Methods and Clinical Translational Challenges of Disulfidptosis in Cancer.Cells · 2026Review
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Multi-omics and spatial transcriptomics decode the ZDHHC9-driven hypoxia-immunosuppressive axis in hepatocellular carcinoma.Frontiers in oncology · 2026Article
- The emerging role of ZDHHC9 in cancer: from protein palmitoylation to tumor progression and immune regulation.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Identifying potential molecular targets for GC liver metastasis (GCLM) may provide new treatment avenues. Initially, using label-free proteomics to screen clinical samples from GCLM patients suggested ASF1B as a possible promoter of GCLM. We further validated this finding with in vitro experiments and spleen injection liver metastasis model, subsequent transcriptome sequencing after ASF1B knockdown revealed SLC7A11-mediated ferroptosis is critical for GCLM progression. Mechanistically, ASF1B recruits and binds to the transcription factor HOXB3, thereby promoting ZDHHC9's transcriptional level. Additionally, ZDHHC9 regulates SLC7A11-mediated ferroptosis in GC cells. Further tumor metastasis assays showed ZDHHC9 promotes peritoneal, pulmonary, and hepatic metastases in GC. Subsequently, immunoprecipitation and LC-MS analyses revealed the molecular interaction between ZDHHC9 and PCBP1. ZDHHC9, a palmitoyltransferase, inhibits ferroptosis by palmitoylating PCBP1. Mechanistically, ZDHHC9 palmitoylates PCBP1 at residue C109, inhibiting PCBP1 ubiquitination and thereby suppressing SLC7A11-mediated ferroptosis. In line with this, further experiments showed PCBP1 regulates ferroptosis by modulating SLC7A11 RNA stability. Finally, IHC and immunofluorescence revealed significant clinical correlations among ASF1B, ZDHHC9, PCBP1, and SLC7A11. Additionally, this signaling axis is strongly associated with PD-L1 expression. In conclusion, this study demonstrates ASF1B promotes GC liver metastasis by inhibiting ferroptosis via the ZDHHC9/PCBP1/SLC7A11 axis, providing a potential immunotherapeutic target for GCLM.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.