Elucidating the multiscale mechanisms and therapeutic targets of caffeic acid in gastric cancer: a synergy of computational and experimental approaches.

IF 3.9 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Frontiers in Molecular Biosciences Pub Date : 2025-10-01 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1663517
Hongrong Zhang, Yufan Li, Ya Li
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引用次数: 0

Abstract

Introduction: Gastric cancer is a malignant tumor with high incidence and mortality rates worldwide, and effective therapeutic strategies targeting its complex pathological processes are limited. Caffeic acid is a phenolic compound derived from natural plants and has attracted attention for its potential anticancer properties; however, its mechanism of action in gastric cancer has not been fully elucidated.

Methods: In this study, a multimodal computational framework integrating multiomics, machine learning, and molecular dynamics simulations, combined with in vitro experiments, was used to systematically investigate the molecular mechanism of caffeic acid against gastric cancer.

Results: Among the predicted targets, FZD2-a major receptor that mediates noncanonical WNT/Ca2+ signaling-was identified as a core regulatory hub associated with tumor progression and metastasis. Molecular dynamics simulations further revealed a stable binding interaction between caffeic acid and FZD2. An in vitro EMT model was established by treating human gastric cancer cells with TGF-β1. The results showed that caffeic acid intervention inhibited cell migration, invasion, and EMT progression while reducing FZD2 protein expression.

Discussion: This study confirmed that caffeic acid regulates FZD2 expression and inhibits the activation of the noncanonical Wnt5a/Ca2+/NFAT signaling pathway, thereby interfering with gastric cancer-related pathological processes. These findings reveal the molecular mechanism of caffeic acid in gastric cancer and reflect the value of natural products in cancer research.

阐明咖啡酸在胃癌中的多尺度机制和治疗靶点:计算和实验方法的协同作用。
胃癌是世界范围内发病率和死亡率高的恶性肿瘤,针对其复杂病理过程的有效治疗策略有限。咖啡酸是一种从天然植物中提取的酚类化合物,因其潜在的抗癌特性而备受关注;然而,其在胃癌中的作用机制尚未完全阐明。方法:本研究采用多模态计算框架,结合多组学、机器学习和分子动力学模拟,结合体外实验,系统探讨咖啡酸抗胃癌的分子机制。结果:在预测的靶点中,fzd2 -一种介导非典型WNT/Ca2+信号的主要受体-被确定为与肿瘤进展和转移相关的核心调节枢纽。分子动力学模拟进一步揭示了咖啡酸与FZD2之间稳定的结合相互作用。用TGF-β1治疗人胃癌细胞,建立体外EMT模型。结果表明,咖啡酸干预可抑制细胞迁移、侵袭和EMT进展,同时降低FZD2蛋白表达。讨论:本研究证实咖啡酸调节FZD2表达,抑制非规范Wnt5a/Ca2+/NFAT信号通路的激活,从而干扰胃癌相关病理过程。这些发现揭示了咖啡酸在胃癌中的分子机制,反映了天然产物在癌症研究中的价值。
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
Frontiers in Molecular Biosciences
Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
7.20
自引率
4.00%
发文量
1361
审稿时长
14 weeks
期刊介绍: Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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