NINJ1 in regulated cell death and cancer: a plasma membrane rupture executor with dual roles in tumor progression

Abstract

To elucidate the molecular structure, oligomerization mechanisms, and roles of Ninjurin-1 (NINJ1) in regulated cell death (RCD) pathways (pyroptosis, necroptosis, ferroptosis, secondary necrosis, PANoptosis) and its dual role in cancer (tumor suppressor vs. pro-tumor factor). Systematic literature review and analysis of NINJ1’s functions across RCD types, cancer progression, and immune modulation. NINJ1 mediates plasma membrane rupture (PMR) and intracellular content release, dictating inflammatory responses. In cancer, it induces immunogenic cell death (suppressor) but drives chronic inflammation and immunosuppression in tumors (promoter). Context-dependent mechanisms (e.g., p53–NINJ1–xCT axis) regulate its effects, influencing metastasis and immune cell trafficking.