In this study, we found that ECD was overexpressed in GC, especially in metastatic GC, and ECD promotes GC invasion and metastasis by stabilizing hnRNP F. We further found that ZFP91 is the E3 ligase responsible for hnRNP F ubiquitination at Lys 185 and degradation. Here, ZFP91 is linked to gastric cancer.