POU6F2 promotes liver metastasis of gastric adenocarcinoma by dual mechanism of transcriptional upregulation of SNAI1 and IGF2/PI3K/AKT signaling-induced conversion of hepatic stellate cells into cancer-associated fibroblasts

被引：0

作者：

Yang, Chunxiao ^{[1
,2
]}

Gao, Zhiqing ^{[2
,3
]}

Tang, Ruiming ^{[1
]}

Zhou, Lihuan ^{[1
]}

Zhou, Ping ^{[2
]}

Shi, Wangpan ^{[4
]}

Ren, Dong ^{[5
]}

Chen, Han ^{[1
,2
]}

Zhang, Zhuojun ^{[1
,2
]}

Xie, Xiaoyi ^{[1
,2
]}

Lin, Jiaqian ^{[1
,2
]}

Ye, Yingming ^{[6
]}

Feng, Zhengfu ^{[1
]}

Feng, Xiaoli ^{[1
]}

He, Yaoming ^{[7
]}

Zhi, Yaofeng ^{[8
]}

Liu, Dongmei ^{[8
]}

Zhang, Xin ^{[8
]}

Jiang, Lili ^{[1
,2
]}

机构：

[1] Guangzhou Med Univ, Affiliated Qingyuan Hosp, Qingyuan Peoples Hosp, Qingyuan, Peoples R China

[2] Guangzhou Med Univ, Guangzhou Municipal & Guangdong Prov Key Lab Prot, Guangzhou, Peoples R China

[3] Southern Med Univ, Sch Basic Med, Dept Mol Med, Guangzhou, Peoples R China

[4] Univ Calif San Diego Hlth Syst, Dept Pathol, San Diego, CA USA

[5] Univ Calif Irvine, Dept Pathol, Med Ctr, Orange, CA USA

[6] Guangdong Pharmaceut Univ, Sch Basic Courses, Dept Pathogen Biol & Immunol, Guangzhou, Peoples R China

[7] Jiangmen Cent Hosp, Dept Gastrointestinal Surg, Jiangmen, Peoples R China

[8] Guangdong Med Univ, Jiangmen Cent Hosp, Clin Expt Ctr,Jiangmen Clin Med Coll, Jiangmen Key Lab Precis & Clin Translat Med, Jiangmen, Peoples R China

来源：

BRITISH JOURNAL OF CANCER | 2025年 / 133卷 / 01期

关键词：

HEPATOCELLULAR-CARCINOMA; EXPRESSION; BETA; GENE;

D O I：

10.1038/s41416-025-03017-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundActivation of cancer-associated fibroblasts (CAFs) plays an important role in tumor metastasis. The purpose of this study is to investigate the role of POU6F2 in conversion of hepatic stellate cells (HSCs) into CAFs in liver metastasis of gastric adenocarcinoma (GAC).MethodsPOU6F2 expression was examined by real-time PCR, Western blot and immunohistochemical staining. The functional roles of POU6F2 in GAC liver metastasis were investigated both cellular experiments in vitro and in vivo using a mouse model of subcutaneous splenic injection. ChIP and ELISA assays were used to explore the underlying molecular mechanism of POU6F2 in liver metastasis of GAC.ResultsHere we reported that POU6F2 was upregulated in GAC tissue with liver metastasis, which predicted poor early liver metastasis. Upregulating POU6F2 promoted EMT, invasion and migration of GAC cells in vitro, and the liver metastasis of GAC cells in vivo. Mechanic investigation further revealed that upregulating POU6F2 promoted the invasion and metastasis of GAC by transcriptional upregulation of EMT-inducer SNAI1, and promoting the conversion of HSCs into CAFs dependent on transcriptional upregulation of IGF2-induced activation of PI3K/AKT signaling.ConclusionOur findings uncover a novel dual mechanism by which POU6F2 promotes liver metastasis of GAC.

引用

页码：14 / 26

页数：13

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