NEDD8-conjugating enzyme E2 UBE2F deficiency promotes lung cancer metastasis by stabilizing Snail

Abstract

Abstract Lung cancer is the most prevalent malignant tumor, resulting in the highest morbidity and mortality rates worldwide. Approximately 30–40% of lung cancer cases progress to distant metastasis, significantly affecting patient quality of life and survival. However, the mechanisms driving this metastasis remain incompletely understood. Our study aims to investigate the impact of the NEDD8-conjugating enzyme UBE2F on lung cancer metastasis. We established a nude mouse model of lung cancer metastasis with stably silencing the UBE2F protein of human lung cancer cells by tail vein injection. In in vivo animal experiments, we observed a significant increase in the number of metastatic micronodules on the lung surface of nude mice following UBE2F knockout compared to the control group. Moreover, the results of cell scratch and transwell chamber assays indicated that UBE2F knockout enhanced the invasion and migration capabilities of lung cancer cells. Western blot analysis further revealed that UBE2F knockout impeded the degradation of Snail protein, a critical factor in epithelial-mesenchymal transition (EMT), resulting in its accumulation. Together, these findings suggested that the downregulation of UBE2F expression inhibits the degradation of Snail protein, thereby promoting the invasion and metastasis of lung cancer cells.