NEDD4L Regulates the Proliferation and Metastasis of Non-small-cell Lung Cancer by Mediating CPNE1 Ubiquitination

Abstract

High expression of CPNE1 is positively correlated with the occurrence, TNM stage, lymph node metastasis, and distant metastasis of non-small-cell lung cancer (NSCLC), suggesting that CPNE1 may be an effective target for the treatment of NSCLC. No direct role of post-translational modification of CPNE1 in NSCLC has been reported. This study confirms that CPNE1 is degraded by two pathways: the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. CPNE1 binds with the ubiquitin molecule via its K157 residue. Moreover, we determine that the ubiquitin ligase NEDD4L can mediate the ubiquitination of CPNE1 and promote its degradation. In addition, we find that NEDD4L knockout promotes the proliferation and metastasis of NSCLC cells by regulating CPNE1. This study aims to further investigate the mechanism of CPNE1 ubiquitination in the occurrence and development of NSCLC and provide a new potential target for NSCLC treatment.