文献类型：期刊文献

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

作者：Jia, Yanjuan[1,2,3];Li, Yaling[1,2];Li, Yan[4];Li, Yonghong[2,3];Qu, Tao[2,3];Fu, Zhuomin[2,3];Ma, Yuanyuan[5];Li, Zhenhao[2,3];Wang, Wanxia[2,3];Yu, Miao[2,3];Jin, Xiaojie[1];Gao, Xiaoling[6];Liu, Yongqi[1]

第一作者：Jia, Yanjuan

通信作者：Liu, YQ[1];Gao, XL[2]

机构：[1]Gansu Univ Chinese Med, Minist Educ, Dunhuang Key Lab Med & Transformat, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Prov Hosp, Inst Clin Res & Translat Med, Lanzhou 730000, Gansu, Peoples R China;[4]Chongqing Acad Chinese Mat Med, Chongqing Coll Tradit Chinese Med, Chongqing 400065, Peoples R China;[5]Xian Daxing Hosp, Dept Crit Care Med 2, Xian 710000, Shanxi, Peoples R China;[6]Hainan Med Univ, Hainan Gen Hosp, Hainan Affiliated Hosp, Clin Lab Ctr, Haikou 570100, Hainan, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Minist Educ, Dunhuang Key Lab Med & Transformat, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Hainan Med Univ, Hainan Gen Hosp, Hainan Affiliated Hosp, Clin Lab Ctr, Haikou 570100, Hainan, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：23

期号：1

外文期刊名：JOURNAL OF TRANSLATIONAL MEDICINE

收录：;Scopus(收录号：2-s2.0-105012156288);WOS:【SCI-EXPANDED(收录号:WOS:001539742200003)】；

基金：We sincerely thank Prof. Yong An, Prof. Peng Wang, and Prof. Jianzhen He of Gansu University of Chinese Medicine, Prof. Hailong Zhang of Lanzhou University, for their valuable guidance in study design. We also extend our gratitude to Dr. Daqin Suo of Sun Yat-sen University Cancer Center, Dr. Li Wang of Gansu Central Hospital, and Dr. Jian Yang and Dr. Ling Wang of Gansu Provincial Hospital for their methodological support. The graphical abstract was created using Figdraw (www.figdraw.com, ID: RPTRY9BB66).

语种：英文

外文关键词：Gastric cancer; PYGO1; M2 macrophage infiltration; ITGB1/CD47 axis; Pentagalloylglucose

摘要：BackgroundGastric 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.MethodsBioinformatics 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.ResultsPYGO1 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 PYGO1-H3K4me2/3 interaction, suppressing the ITGB1/CD47 axis and GC malignancy.ConclusionsOur study demonstrates the oncogenic role of PYGO1 in GC and identifies PGG as a potential inhibitor, highlighting the PYGO1/ITGB1/CD47 axis as a promising therapeutic target for GC.