Downregulation of TIMP1 Promotes Ferroptosis and Suppresses Proliferation and Migration of Gastric Cancer Cells via Modulation of the PI3K/AKT Pathway.

IF 2.5 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2026-06-09 DOI:10.2174/0115680096437140260605102156

Yan Kang, Yaoqi Li, Tianxiang Liu, Chenglou Zhu, Junfeng Ma

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引用次数: 0

Abstract

Introduction: Tissue inhibitor of metalloproteinase 1 (TIMP1) is essential for the development and progression of various cancers and represents a valuable prognostic indicator.

Methods: The present study utilized in vitro experimental models and comprehensive bio-informatics analyses to systematically investigate the biological function of TIMP1 in gastric cancer.

Results: We found a positive correlation between TIMP1 expression and clinical stage in gastric cancer patients. Silencing of the TIMP1 gene markedly impaired the proliferative, invasive, and migratory capacities of gastric cancer cells. Furthermore, downregulation of TIMP1 could retard gastric cancer progression by suppressing the PI3K/AKT signaling pathway, thereby triggering lipid peroxidation and ferroptosis in gastric cancer cells.

Discussion: This study reveals that TIMP1 serves as a key regulator of ferroptosis in gastric cancer cells. Specifically, downregulation of TIMP1 inhibits the PI3K/AKT signalling pathway, reduces the intracellular antioxidant defense capacity (e.g., GPX4 and SLC7A11 expression), and consequently induces ferroptosis, accompanied by the suppression of malignant tumour phenotypes.

Conclusion: This suggests that TIMP1 could serve as a novel biomarker, offering new perspectives on the molecular mechanisms underlying gastric cancer and its treatment.

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TIMP1的下调通过调控PI3K/AKT通路促进胃癌细胞凋亡并抑制其增殖和迁移。

组织金属蛋白酶1抑制剂（TIMP1）在各种癌症的发生和进展中至关重要，是一种有价值的预后指标。方法：本研究采用体外实验模型和综合生物信息学分析，系统研究TIMP1在胃癌中的生物学功能。结果：TIMP1的表达与胃癌患者的临床分期呈正相关。TIMP1基因的沉默明显损害了胃癌细胞的增殖、侵袭和迁移能力。此外，下调TIMP1可通过抑制PI3K/AKT信号通路延缓胃癌进展，从而引发胃癌细胞脂质过氧化和铁下垂。讨论：本研究揭示TIMP1是胃癌细胞铁下垂的关键调节因子。具体来说，TIMP1下调可抑制PI3K/AKT信号通路，降低细胞内抗氧化防御能力（如GPX4和SLC7A11的表达），从而诱导铁凋亡，同时抑制恶性肿瘤表型。结论：TIMP1可能作为一种新的生物标志物，为研究胃癌的分子机制和治疗提供了新的视角。

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

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.