ASF1B promotes gastric cancer liver metastasis through inhibiting ZDHHC9/PCBP1/ SLC7A11 signaling axis mediated ferroptosis.

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, immu

SUBMITTER: Wang M 

PROVIDER: S-EPMC12905238 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature