LAUSR

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying GC cell proliferation are largely unclear. Here, we showed that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted GC cell proliferation partially through inhibition of Gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in GC. Mechanistically, GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7 resulting in SCFFBXW7-mediated ubiquitination and degradation. A non-degradable GFI1 S94A/S98A mutant was more potent in driving GC cell proliferation and tumorigenesis than wild type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7.