BATF2 inhibits the stem cell-like properties and chemoresistance of gastric cancer cells through PTEN/AKT/β-catenin pathway

被引:0
作者
Cao, Longlong [1 ,2 ,3 ]
Weng, Kai [1 ,2 ,3 ]
Li, Lujie [1 ,2 ,3 ]
Lin, Guangtan [1 ,2 ,3 ]
Zhao, Yuxuan [1 ,2 ,3 ]
Gao, Youxin [1 ,2 ,3 ]
Huang, Xiaobo [1 ,2 ,3 ]
Chen, Qiyue [1 ,2 ,3 ]
Wang, Jiabin [1 ,2 ,3 ]
Zheng, Chaohui [1 ,2 ,3 ]
Huang, Changming [1 ,2 ,3 ]
Xi, Jianwei [1 ,2 ,3 ]
Li, Ping [1 ,2 ,3 ]
机构
[1] Fujian Med Univ, Dept Gastr Surg, Union Hosp, 29 Xinquan Rd, Fuzhou 350001, Fujian Province, Peoples R China
[2] Fujian Med Univ, Key Lab Gastrointestinal Canc, Minist Educ, Fuzhou 350001, Fujian, Peoples R China
[3] Fujian Med Univ, Fujian Key Lab Tumor Microbiol, Fuzhou 350001, Fujian, Peoples R China
来源
THERANOSTICS | 2024年 / 14卷 / 18期
基金
中国国家自然科学基金;
关键词
PROMOTES; AP-1; METHYLATION;
D O I
10.7150/thno.98389
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Gastric cancer (GC) ranks as the fifth leading cause of cancer mortality, with cancer stem cells (CSCs) playing a critical role in tumor progression and resistance to chemotherapy. Conventional chemotherapy often fails to effectively target these stem cells. BATF2, a tumor suppressor, is known for its role in gastric cancer, but its influence on cancer stem cell-like properties and chemotherapy response remains unclear. Methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed on 9 gastric cancer samples to evaluate the expression and regulatory function of BATF2. In vitro experiments involving cell cultures, tumor cell spheroids, and organoids were conducted to assess BATF2's impact on 5-Fu sensitivity and its interaction with drug transporters and signaling pathways. In vivo studies, including subcutaneous tumor formation assays, immunohistochemistry, and immunoblotting, were used to validate findings. Results: BATF2 was confirmed as a tumor suppressor in gastric cancer through scRNA-seq analysis. Elevated BATF2 expression correlated with improved outcomes from postoperative chemotherapy in GC patients and increased sensitivity to 5-Fu. BATF2 enhanced 5-Fu responsiveness by inhibiting the ABCG2 drug transporter and promoting PTEN stability, which suppressed AKT phosphorylation. This led to reduced nuclear (3-catenin levels and decreased expression of stem cell markers CD44, SOX2, and NANOG, ultimately reducing chemoresistance and stem-like properties in GC cells. Conclusions: BATF2 plays a pivotal role in regulating stem-like characteristics and chemoresistance in gastric cancer through the BATF2/PTEN/AKT/ABCG2 pathway. These findings suggest a novel therapeutic strategy targeting BATF2 to enhance chemotherapy effectiveness in gastric cancer treatment.
引用
收藏
页码:7007 / 7022
页数:16
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