Vacuole protein sorting 18 (Vps18) suppresses epithelial growth factor receptor (EGFR) expression and lung tumorigenesis.

Lung cancer remains the leading cause of cancer-related deaths worldwide. While lysosomal degradative function is critical for cellular homeostasis, its role in lung cancer pathogenesis remains poorly understood. Here, we identify Vps18 as an important tumor suppressor in murine lung tumorigenesis. Genetic ablation of Vps18 accelerates lung tumorigenesis in LSL-K-Ras mice, accompanied by enhanced tumor cell proliferation. Mechanistically, Vps18 deficiency elevates EGFR protein levels and activates the ERK-MAPK signaling pathway in lung tumors. Strikingly, expression of dominant-negative EGFR (dnEGFR) partially suppresses the tumor-promoting effects of Vps18 loss. Our findings unveil a novel Vps18-EGFR-ERK axis in lung cancer and may inform the development of targeted therapeutic strategies.