2. Academic Validation
  3. Ephrin A1 functions as a ligand of EGFR to promote EMT and metastasis in gastric cancer

Ephrin A1 functions as a ligand of EGFR to promote EMT and metastasis in gastric cancer

  • EMBO J. 2025 Jan 21. doi: 10.1038/s44318-025-00363-x.
Shuang Li # 1 2 3 4,  Meng Sun # 1 2 3 4,  Yun Cui # 1 3 4,  Dongyang Guo # 1 3 4,  Feng Yang 2,  Qiang Sun 5,  Yinuo Ding 1 3,  Mengjie Li 1 3,  Yiman Liu 1 4,  Guangshuo Ou 6,  Wei Zhuo 7 8 9,  Tianhua Zhou 10 11 12
Affiliations

Affiliations

  • 1 Department of Colorectal Surgery and Oncology and Department of Cell Biology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Binjiang Institute of Zhejiang University, Hangzhou, China.
  • 3 Cancer Center of Zhejiang University, Hangzhou, China.
  • 4 Institute of Gastroenterology, Zhejiang University School of Medicine, Hangzhou, China.
  • 5 International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
  • 6 School of Life Sciences, Tsinghua University, Beijing, China.
  • 7 Department of Colorectal Surgery and Oncology and Department of Cell Biology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. wzhuo@zju.edu.cn.
  • 8 Cancer Center of Zhejiang University, Hangzhou, China. wzhuo@zju.edu.cn.
  • 9 Institute of Gastroenterology, Zhejiang University School of Medicine, Hangzhou, China. wzhuo@zju.edu.cn.
  • 10 Department of Colorectal Surgery and Oncology and Department of Cell Biology, Center for Medical Research and Innovation in Digestive System Tumors, Ministry of Education, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. tzhou@zju.edu.cn.
  • 11 Cancer Center of Zhejiang University, Hangzhou, China. tzhou@zju.edu.cn.
  • 12 Institute of Gastroenterology, Zhejiang University School of Medicine, Hangzhou, China. tzhou@zju.edu.cn.
  • # Contributed equally.
PMID: 39838173 DOI: 10.1038/s44318-025-00363-x
Abstract

Distant metastasis is the major cause of gastric Cancer mortality, and epidermal growth factor receptor (EGFR) activation plays critical roles in gastric Cancer dissemination. However, EGFR targeting therapies in gastric Cancer show only marginal effects, and the molecular mechanisms of oncogenic EGFR signaling remain poorly defined. Here, we report Ephrin A1 as a novel ligand of EGFR in gastric Cancer. Ephrin A1 facilitates colonization and metastasis of gastric Cancer cells in vitro and in vivo via inducing epithelial-mesenchymal transition (EMT). Ephrin A1 directly interacts with EGFR and induces EGFR dimerization, phosphorylation and activation of downstream signaling. Ephrin A1-induced EMT can be rescued by EGFR signaling inhibitors or knockout of EGFR, but not depletion of its classical receptor EphA2. Moreover, Ephrin A1 protein level correlates with EGFR phosphorylation levels in gastric Cancer patients. Collectively, our work uncovers Ephrin A1 as a functional ligand of EGFR and highlights the potential role of the Ephrin A1/EGFR/EMT regulatory axis in Cancer metastasis.

Keywords

EGFR; EMT; Ephrin A1; Gastric Cancer; Metastasis.

Figures
Products
Inhibitors & Agonists
Other Products