TRAF3IP3 Induces ER Stress‐Mediated Apoptosis with Protective Autophagy to Inhibit Lung Adenocarcinoma Proliferation

• DOI: 10.1002/advs.202411020
• Publication Date: 2025-03-11T20:06:17Z
• Authors: Guang Zhao; Jun Qi; Fang Li; Haotian Ma; Rui Wang; Xiuyi Yu; Yufei Wang; Sida Qin; Jie Wu; Chen Huang; Hong Ren; Boxiang Zhang

Abstract TNF receptor‐associated factor 3 interacting protein (TRAF3IP3/T3JAM) exhibits dual roles in cancer progression. While upregulated most malignancies and critical for immune regulation. However, the specific effects molecular mechanisms of TRAF3IP3 on progression lung adenocarcinoma (LUAD) remains poorly understood. This study reveals is several tumor tissues but exclusively decreased LUAD Lung squamous cell carcinoma (LUSC) tissues, consequential a favorable overall survival (OS) rather than LUSC. Herein, it reported that can suppress proliferation promote apoptosis rate cells by inducing excessive ER stress‐related apoptosis. Importantly, triggers stress via PERK/ATF4/CHOP pathway, accompanied stimulated stress‐induced cytoprotective autophagy cells. Through IP‐MS analysis, STRN3 identified as direct downstream interactor with corroborated to regulate positively. Mechanistically, facilitates recruitment lumen through its transmembrane domain fulfills functional role an STRN3‐dependent manner Given orchestrating stress‐associated fate determination, importance highlighted novel therapeutic target treatment.