LPIN1 exerts tumor-suppressive functions in HNSCC through autophagy-mediated inhibition of proliferation and metastasis

Recent studies highlight the magnesium-dependent phosphatidate phosphatase LPIN1 as a key regulator of tumor progression; however, its specific role and molecular mechanisms in head and neck tumors (including nasopharyngeal carcinoma and conventional head and neck squamous cell carcinoma, HNSCC) remain elusive. In this study, integrated bioinformatic analyses using GEO, TCGA, UALCAN, and Kaplan–Meier Plotter databases revealed that LPIN1 is significantly downregulated in HNSCC tissues and its low expression correlates with poor patient survival. Functional assays in both C666-1 and CNE-3 nasopharyngeal carcinoma (NPC) cell lines demonstrated that LPIN1 overexpression markedly suppresses proliferation, migration, and invasion. Mechanistically, LPIN1 induces cytostatic autophagy, evidenced by increased LC3-II/LC3-I ratio, enhanced autophagosome formation, and elevated autophagic flux assessed by LC3B immunofluorescence staining. Crucially, genetic silencing of ATG5 or pharmacological inhibition with 3-methyladenine (3-MA) significantly attenuated the tumor-suppressive effects of LPIN1 , confirming autophagy as an essential mediator. Furthermore, in vivo xenograft models validated that LPIN1 overexpression significantly inhibits tumor growth. Collectively, this study identifies LPIN1 as a novel prognostic biomarker and establishes the LPIN1 –autophagy axis as a potential therapeutic vulnerability for autophagy-modulating strategies in head and neck tumors (including NPC and HNSCC).