Translational cancer research · 2026
AMOT mediates YAP1 activation and promotes the cell progression and glycolysis in non-small cell lung cancer by modulating the Hippo signaling pathway.
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Guo Yihao, Wang Wendong, Li Jinsong, Zhang Jun
Аннотация
BACKGROUND: Non-small cell lung cancer (NSCLC) exhibits aggressive cell progression and profound metabolic reprogramming. This study investigated the clinical significance, functional role, and molecular mechanism of the Angiomotin (AMOT)/Yes-associated protein 1 (YAP1)/Hippo axis in regulating NSCLC growth and glycolysis.
METHODS: AMOT expression was analyzed in 68 paired NSCLC and adjacent normal tissues. In vitro gain- and loss-of-function assays (proliferation, apoptosis, and Transwell migration) and normalized intracellular metabolic measurements (ATP, lactate, and glucose) were performed in A549 and NCI-H1299 cell lines. The underlying Hippo signaling mechanism was evaluated via Co-IP, Western blotting, The Cancer Genome Atlas (TCGA) correlation analysis, and subcutaneous xenograft mouse models.
RESULTS: AMOT was significantly upregulated in NSCLC tissues, correlating with larger tumor size (≥4 cm), advanced clinical stage, and poorer overall survival. AMOT silencing markedly suppressed cell proliferation and migration while inducing apoptosis. AMOT and YAP1 exhibited a strong positive co-expression pattern. YAP1 knockdown significantly inhibited proliferation, migration, intracellular glycolysis, and in vivo tumor growth, effects that were partially rescued by AMOT overexpression. Mechanistically, AMOT inhibited LATS1 and YAP1 phosphorylation, promoting YAP1 stabilization and nuclear transactivation, thereby driving tumor progression and glycolytic reprogramming.
CONCLUSIONS: The AMOT/YAP1/Hippo axis acts as a crucial driver of NSCLC progression and aerobic glycolysis, offering a promising therapeutic target for NSCLC intervention.
METHODS: AMOT expression was analyzed in 68 paired NSCLC and adjacent normal tissues. In vitro gain- and loss-of-function assays (proliferation, apoptosis, and Transwell migration) and normalized intracellular metabolic measurements (ATP, lactate, and glucose) were performed in A549 and NCI-H1299 cell lines. The underlying Hippo signaling mechanism was evaluated via Co-IP, Western blotting, The Cancer Genome Atlas (TCGA) correlation analysis, and subcutaneous xenograft mouse models.
RESULTS: AMOT was significantly upregulated in NSCLC tissues, correlating with larger tumor size (≥4 cm), advanced clinical stage, and poorer overall survival. AMOT silencing markedly suppressed cell proliferation and migration while inducing apoptosis. AMOT and YAP1 exhibited a strong positive co-expression pattern. YAP1 knockdown significantly inhibited proliferation, migration, intracellular glycolysis, and in vivo tumor growth, effects that were partially rescued by AMOT overexpression. Mechanistically, AMOT inhibited LATS1 and YAP1 phosphorylation, promoting YAP1 stabilization and nuclear transactivation, thereby driving tumor progression and glycolytic reprogramming.
CONCLUSIONS: The AMOT/YAP1/Hippo axis acts as a crucial driver of NSCLC progression and aerobic glycolysis, offering a promising therapeutic target for NSCLC intervention.