Authors
Lei Gao, Qinying Han, Yunpeng Wang, Xuemei Li, Bofang Wang, Baohong Gu, Weidong Li, Lin Xiang, Ying Zhang, Hao Chen
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e77095. Aug 17, 2026. Epub Aug 17, 2026.
Abstract
Coagulation factor VII (F7) has been implicated in tumor progression; however, its role in gastric cancer metastasis and immune evasion remains incompletely understood. In this study, we identified F7 as a clinically relevant driver of gastric cancer. F7 was highly expressed in tumor tissues and closely associated with lymph node metastasis, poor prognosis, and reduced CD8+ T-cell infiltration. Tumor-derived autocrine F7 interacted with ITGA2 on the cancer cell surface and activated ITGA2-associated FAK-NF-κB signaling and promoted invasion, migration, and anoikis resistance. F7 induced PD-L1 expression in a manner partly dependent on ITGA2-mediated PI3K-AKT signaling and promoted collagen I deposition in liver metastatic lesions, which was associated with reduced CD8+ T-cell infiltration. Co-immunoprecipitation showed that the K1.2 and K1.3 regions of F7 mediated its interaction with the N-terminal extracellular region of ITGA2. Further investigations identified HNF4A as an upstream transcription factor of F7, with anoikis-associated stress enhancing HNF4A nuclear accumulation and F7 transcription. Notably, ThonningianinA (THA) was identified as a potential F7-targeting small molecule that suppressed F7-associated malignant phenotypes, reduced tumor growth, and enhanced the antitumor efficacy of anti-PD-1 therapy. These findings support F7 as a potential therapeutic target for metastatic gastric cancer.
PMID:
42606136
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 5
- Comments 0