MISP promotes the progression of lung adenocarcinoma through Inhibition of the Hippo signaling pathway.

BACKGROUND: Globally, lung cancer is a malignant tumor with the highest morbidity and mortality rate, of which lung adenocarcinoma (LUAD) is the most common pathological type, accounting for about 40% of all cases. This study aims to investigate the impact and molecular mechanisms of mitotic spindle positioning (MISP) on the occurrence and progression of LUAD. METHODS: The expression level of MISP were evaluated by qPCR and Western blotting. Hippo signaling-related protein levels were measured by Western blotting. Co-immunoprecipitation assay was applied to assess the interaction between MISP and MST1. The roles of MISP in LUAD cells were determined through CCK-8 assay, transwell migration/invasion assay, and flow cytometric analysis. A xenograft tumor model (n = 6) was established to calculate the effect of MISP in vivo. RESULTS: MISP expression was significantly higher in LUAD tissues compared to normal tissues. MISP overexpression promoted LUAD cell proliferation and migration in in vitro models, as well as tumor growth and metastasis in LUAD animal models. Western blotting demonstrated that MISP overexpression increased the expression of YAP, TAZ and CYR61, and decreased the expression of MST1 and phosphorylated YAP, thereby blocking the Hippo signaling pathway. While MISP knockdown had the opposite effect. Mechanistic experiments revealed that MISP directly interacts with MST1, thereby inhibiting Hippo signaling. CONCLUSIONS: In conclusion, our study reveals a novel discovery that MISP promotes the growth and invasion of LUAD cells by interacting with MST1 and suppressing the Hippo pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03773-9.