WWP2 promotes the proliferation and metastasis of NSCLC through Hippo pathway and Wnt pathway

WWP2 (WW domain-containing E3 ubiquitin protein ligase 2), a member of the HECT family of E3 ubiquitin ligases, contains four WW domains and is frequently overexpressed in non-small-cell lung cancer (NSCLC). Its expression is closely associated with advanced TNM stage, lymph node metastasis and poor overall survival, indicating strong clinical relevance. Through both gain-of-function and loss-of-function experiments, we demonstrated that WWP2 enhances the proliferation and invasion capabilities of NSCLC cells. Mechanistically, WWP2 regulates the subcellular localization of NF2 (merlin), leading to inhibition of the Hippo signalling pathway and subsequent activation of YAP. These findings establish WWP2 as an important oncoprotein that drives NSCLC progression through the Hippo pathway and highlight its potential as a prognostic biomarker and therapeutic target for NSCLC treatment.