Abstract

RASSF1A is a well-established tumor suppressor implicated in various human malignancies; however, its specific role in the metastasis of gastric cancer (GC) remains poorly understood. In this study, we observed that RASSF1A expression is frequently silenced in GC tissues compared to adjacent normal tissues, with its loss significantly correlating with metastatic progression. Immunohistochemical analysis further revealed a negative correlation between RASSF1A levels and the infiltration of neutrophils, as well as the formation of neutrophil extracellular traps (NETs). Mechanistically, knockdown of RASSF1A triggers the JNK-JUN signaling pathway, which subsequently accelerates ribosome biogenesis. This metabolic shift enhances the translation of pro-inflammatory chemokines, thereby promoting neutrophil recruitment and NETs formation. Furthermore, our findings demonstrate that RASSF1A interacts with LTBR, effectively inhibiting the LIGHT-induced recruitment of TRAF2 and suppressing downstream JNK-JUN activation. Collectively, our results suggest that RASSF1A functions as a critical inhibitor of GC metastasis by modulating the chemokine-neutrophil axis, offering novel insights into its role as a therapeutic target in GC.