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| 蛋白质翻译后修饰调控胃癌铁死亡的关键机制、串扰及研究进展 |
| Key Mechanisms, Crosstalk and Research Advances of Protein Post-Translational Modifications in Regulating Ferroptosis in Gastric Cancer |
| 投稿时间：2026-04-12 修订日期：2026-06-23 |
| DOI： |
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| 中文关键词: 胃癌 铁死亡 蛋白质翻译后修饰 泛素化 磷酸化 棕榈酰化 乳酸化 化疗耐药 |
| 英文关键词:Gastric cancer Ferroptosis Protein post?translational modifications Ubiquitination Phosphorylation Palmitoylation Lactylation Chemotherapy resistance |
| 基金项目:内蒙古自治区自然科学基金(2025ZD009) |
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| 摘要点击次数: 60 |
| 全文下载次数: 1 |
| 中文摘要: |
| 胃癌为高发消化道恶性肿瘤，化疗耐药与远处转移是临床治疗主要瓶颈。铁死亡是一类铁离子依赖、脂质过氧化累积介导的程序性细胞死亡，广泛参与胃癌增殖、侵袭、转移及化疗耐药进程。蛋白质翻译后修饰（Post-translational modifications, PTMs）作为蛋白质功能的核心调控方式，可通过泛素化、磷酸化、棕榈酰化、乳酸化等共价修饰，动态调控铁死亡核心蛋白的稳定性、活性及相互作用，进而决定胃癌细胞铁死亡敏感性。当前相关研究已突破单修饰、单靶点的线性研究思路，聚焦多修饰交叉串扰调控网络。本文系统梳理铁死亡调控通路，阐释各类PTMs调控胃癌铁死亡的分子机制与串扰规律，总结当前研究进展并展望未来方向，为开发靶向PTMs–铁死亡轴的胃癌治疗策略提供理论参考。 |
| 英文摘要: |
| Gastric cancer is a highly prevalent malignant tumor of the digestive tract, with chemoresistance and distant metastasis serving as the major bottlenecks in its clinical treatment. Ferroptosis is an iron-dependent form of programmed cell death mediated by the accumulation of lipid peroxides, which is extensively involved in the proliferation, invasion, metastasis and chemoresistance of gastric cancer. As core regulatory modulators of protein function, protein post-translational modifications (PTMs) dynamically govern the stability, activity and intermolecular interactions of key ferroptosis effector proteins via covalent modifications including ubiquitination, phosphorylation, palmitoylation and lactylation, thereby determining the ferroptotic sensitivity of gastric cancer cells. Recent relevant studies have moved beyond the linear research paradigm focusing on single modification and single target, and shifted their focus to the regulatory network of crosstalk among multiple modifications. This paper systematically reviews the regulatory pathways of ferroptosis, elaborates the molecular mechanisms and crosstalk patterns by which various PTMs modulate ferroptosis in gastric cancer, summarizes current research advances and prospects future research directions, and provides theoretical references for developing therapeutic strategies targeting the PTM–ferroptosis axis against gastric cancer. |
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