METTL14-mediated m6A Modification of COL3A1 mRNA Inhibits Gastric Cancer Metastasis via Recognition by YTHDF2

Gastric cancer metastasis remains a leading cause of cancer-related mortality, yet its underlying regulatory mechanisms are not fully understood. The RNA N6-methyladenosine (m⁶A) writer METTL14 serves a context-dependent role in tumor progression. In this study, we identify METTL14 as a crucial metastasis suppressor in gastric cancer and clarify its specific mechanism of action. Through integrated MeRIP-seq and functional analyses, we discovered that METTL14 directs the m⁶A-dependent degradation of COL3A1 mRNA, a previously unrecognized key driver of gastric cancer progression. METTL14 knockdown markedly enhanced tumor invasion, migration, proliferation, and stem-like properties in vitro and promoted metastasis in vivo, which were all effectively reversed by concurrent COL3A1 silencing. Mechanistically, METTL14-mediated suppression of COL3A1 required recognition by the m⁶A reader YTHDF2, establishing a complete METTL14/YTHDF2-COL3A1 regulatory axis. Our findings not only resolve the context-dependent role of METTL14 in gastric cancer but also reveal a therapeutically targetable axis for combating metastasis.