In this study, we found that EGR4+ cancer cells play a pivotal role in GC metastasis by upregulating GDF15, which can bind ErbB3 to enhance ErbB3/ErbB1 hetero-dimerization and the activation of ErbB1 and its downstream MAPK/ERK and PI3K/AKT signaling, while induce CAFs activation via the TGF-βR pathway to in turn further promote GC metastasis. This evidence concerns the gene EGFR and gastric cancer.