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Peer-reviewedCC BY 4.0Advanced Science

F7 Drives Gastric Cancer Metastasis Through Anoikis Resistance and Tumor Microenvironment Remodeling

  • Lei Gao1
  • Qinying Han1
  • Yunpeng Wang1
  • Xuemei Li1
  • Bofang Wang2
  • Baohong Gu2
  • Weidong Li1
  • Lin Xiang1
  • Ying Zhang3
  • Hao Chen1,2
  1. 1The Second Hospital & Clinical Medical School Lanzhou University Lanzhou People's Republic of China
  2. 2Cancer Center, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai People's Republic of China
  3. 3Department of Laboratory Medicine, the First Medical Centre Chinese PLA General Hospital Beijing People's Republic of China
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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.

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Cite

BibTeXRIS
BibTeX
@article{gao2026drives,
  title = {{F7 Drives Gastric Cancer Metastasis Through Anoikis Resistance and Tumor Microenvironment Remodeling}},
  author = {Lei Gao and Qinying Han and Yunpeng Wang and Xuemei Li and Bofang Wang and Baohong Gu and Weidong Li and Lin Xiang and Ying Zhang and Hao Chen},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.77095},
  url = {https://doi.org/10.1002/advs.77095},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - F7 Drives Gastric Cancer Metastasis Through Anoikis Resistance and Tumor Microenvironment Remodeling
AU  - Lei Gao
AU  - Qinying Han
AU  - Yunpeng Wang
AU  - Xuemei Li
AU  - Bofang Wang
AU  - Baohong Gu
AU  - Weidong Li
AU  - Lin Xiang
AU  - Ying Zhang
AU  - Hao Chen
PY  - 2026
DA  - 2026/08/17
JO  - Advanced Science
DO  - 10.1002/advs.77095
UR  - https://doi.org/10.1002/advs.77095
AB  - 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.
SN  - 2198-3844
ER  -