Fra-1 promotes gastric cancer progression by regulating macrophage polarization and transcriptionally activating HMGA2 expression.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-10-06 DOI:10.1038/s41420-025-02724-1

Feng Zeng, Jiaying Cao, Shan Liao, Yan Chen, Qian He, Yan Lei, Juan Xu, Yanhong Zhou

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引用次数: 0

Abstract

Gastric cancer is a common malignant tumour of gastrointestinal tract with high incidence and low early diagnosis rate. Surgery is its main treatment modality, but some patients have poor prognosis. The rise of immunotherapy provides a new therapeutic strategy for gastric cancer treatment. Elucidating the mechanism of action of immune cells in the tumour microenvironment is the cornerstone for developing new tumour immunotherapy strategies. Previous studies have found that Fra-1 is highly expressed in gastric cancer and is closely associated with macrophage polarisation. In order to further elucidate the specific mechanism, this study firstly used in vitro co-culture experiments to verify that the high expression of Fra-1 in gastric cancer cells induced macrophage M2 polarisation; then, whole proteomics combined with in vitro cellular experiments were used to clarify the specific mechanism by which Fra-1 induced macrophage M2 polarisation by regulating HMGA2 expression in gastric cancer cells. Finally, in vivo experiments further elucidated that Fra-1 induces macrophage polarisation in gastric cancer cells and participates in tumourigenesis and development. The aim of this study was to systematically elucidate the role of Fra-1 in the tumour microenvironment and its possible mechanisms, and to provide an experimental basis for the development of immunotherapeutic strategies for gastric cancer.

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Fra-1通过调控巨噬细胞极化和转录激活HMGA2表达促进胃癌进展。

胃癌是一种常见的胃肠道恶性肿瘤，发病率高，早期诊断率低。手术是其主要治疗方式，但部分患者预后较差。免疫疗法的兴起为胃癌治疗提供了新的治疗策略。阐明免疫细胞在肿瘤微环境中的作用机制是开发新的肿瘤免疫治疗策略的基础。既往研究发现，Fra-1在胃癌中高表达，且与巨噬细胞极化密切相关。为了进一步阐明其具体机制，本研究首先通过体外共培养实验验证了胃癌细胞中Fra-1的高表达诱导巨噬细胞M2极化；然后，采用全蛋白质组学结合体外细胞实验，阐明Fra-1通过调控HMGA2在胃癌细胞中表达诱导巨噬细胞M2极化的具体机制。最后，体内实验进一步阐明了Fra-1在胃癌细胞中诱导巨噬细胞极化，参与肿瘤的发生发展。本研究旨在系统阐明Fra-1在肿瘤微环境中的作用及其可能机制，为胃癌免疫治疗策略的制定提供实验依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.