PYGO1 drives gastric cancer progression via the ITGB1/CD47 axis and is therapeutically targeted by pentagalloylglucose

作者：Yanjuan Jia, Yaling Li, Yan Li, Yonghong Li, Tao Qu, Zhendong Fu, Yuanyuan Ma, Zhenhao Li, Wanxia Wang, Miao Yu, Xiaojie Jin, Xiaoling Gao, Yongqi Liu · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06638-5 · 被引用次数：6 · 研究领域：Phagocytosis and Immune Regulation、Immunotherapy and Immune Responses、Proteoglycans and glycosaminoglycans research

Gastric cancer (GC) represents a significant therapeutic challenge due to its aggressive progression and limited treatment options, emphasizing the urgent need for novel therapeutic targets and strategies. Although PYGO1 functions as a Wnt co-transcriptional activator and chromatin effector, its role in cancer remains poorly characterized. This study aims to elucidate the role of PYGO1 in GC and uncover its regulatory mechanisms. Bioinformatics analysis and immunohistochemistry were used to assess PYGO1 expression in GC tissues and its correlation with prognosis and immune cell infiltration. Cellular and animal models were applied to validate the role of PYGO1 in GC. RNA sequencing, flow cytometry, and immunofluorescence explored the underlying mechanisms. Co-immunoprecipitation coupled with mass spectrometry identified PYGO1-interacting proteins. Molecular docking and molecular dynamics simulations screened and evaluated potential PYGO1 inhibitors. PYGO1 was significantly overexpressed in GC tissues and positively correlated with M2 macrophage infiltration and adverse prognosis. Its knockdown significantly inhibited GC cell proliferation, migration, and invasion in vitro, and reduced tumor growth and metastasis in vivo. Mechanistically, PYGO1 knockdown impaired cell adhesion and disrupted cytoskeletal integrity in GC cells via downregulation of the ITGB1/CD47 axis, mediated by the interaction of PYGO1 with H3K4me2/3, rather than BCL9. Pentagalloylglucose (PGG) disrupted the ...