FKH结构域介导的核FOXP3通过c-MYC/CDKN1A调控、EMT抑制和PI3K/AKT信号调节抑制胃癌恶性肿瘤。

IF 3.7 2区 生物学 Q3 CELL BIOLOGY
Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie
{"title":"FKH结构域介导的核FOXP3通过c-MYC/CDKN1A调控、EMT抑制和PI3K/AKT信号调节抑制胃癌恶性肿瘤。","authors":"Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie","doi":"10.1007/s11010-025-05387-9","DOIUrl":null,"url":null,"abstract":"<p><p>Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation.\",\"authors\":\"Yu Chen, Xia Zhao, Yuze Zhu, Ling Xu, Juanjuan Wang, Zheyi Chen, Hui Chen, Tingting Rong, Yanhui Ma, Yi Liu, Yunlan Zhou, Yingxia Zheng, Lisong Shen, Guohua Xie\",\"doi\":\"10.1007/s11010-025-05387-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.</p>\",\"PeriodicalId\":18724,\"journal\":{\"name\":\"Molecular and Cellular Biochemistry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular and Cellular Biochemistry\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s11010-025-05387-9\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular and Cellular Biochemistry","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s11010-025-05387-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

胃癌(GC)仍然是世界范围内癌症相关死亡的主要原因,特别是在东亚。我们研究了核定位全长FOXP3 (FOXP3FL)作为胃癌肿瘤抑制因子的功能。与邻近正常粘膜相比,GC组织中FOXP3总水平明显降低,胞质和细胞核形态明显不同。功能分析显示,FOXP3FL核过表达在体内和体外均能抑制GC细胞的增殖、迁移和侵袭,促进细胞衰老。机制上,FOXP3FL直接抑制MYC转录并诱导CDKN1A,从而抑制增殖和转移。这些转录变化,以及伴随的PTEN上调和PI3K- p110 α下调,共同减弱了PI3K/AKT信号传导,损害了表达foxp3fl的GC细胞的上皮-间质转化(EMT)。叉头结构域(FKH)是必不可少的:它的缺失产生细胞质FOXP3ΔFKH,失去转录控制和抗肿瘤活性。我们的发现强调了核定位的FOXP3FL作为肿瘤抑制因子,其FKH结构域是其抑制功能的组成部分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FKH domain-mediated nuclear FOXP3 suppresses gastric cancer malignancy via c-MYC/CDKN1A regulation, EMT inhibition, and PI3K/AKT signaling modulation.

Gastric cancer (GC) remains a primary contributor to cancer-associated deaths worldwide, especially in East Asia. We investigated the function of nuclear-localized full-length FOXP3 (FOXP3FL) as an oncosuppressive factor in GC. Total FOXP3 was markedly reduced in GC tissues versus adjacent normal mucosa, with distinct cytoplasmic and nuclear patterns. Functional assays revealed that nuclear overexpression of FOXP3FL suppresses proliferation, migration, and invasion of GC cells in vitro and in vivo and promotes cellular senescence in vivo. Mechanistically, FOXP3FL directly represses MYC transcription and induces CDKN1A, thereby restraining proliferation and metastasis. These transcriptional changes, together with concomitant PTEN upregulation and PI3K-P110α downregulation, collectively attenuate PI3K/AKT signaling and impair epithelial-mesenchymal transition (EMT) in FOXP3FL-expressing GC cells. The forkhead (FKH) domain is essential: its deletion yields cytoplasmic FOXP3ΔFKH, which loses transcriptional control and antitumor activity. Our findings underscore nuclear-localized FOXP3FL as a tumor suppressor whose FKH domain is integral to its suppressive function.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信