Mechanistic study of the Tβ4/SLC7A11 signaling pathway regulating breast cancer evolution

IF 3.7 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-09-03 DOI:10.1016/j.cellsig.2025.112111

Zhaoyan Jin , Hongshu Li , Jiafeng Li , Ying Chang , Zhengri Piao , Quanxin Jin , Tiefeng Jin

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引用次数: 0

Abstract

Thymosin β4 (Tβ4) plays a critical role in breast cancer progression, yet its molecular mechanism remains unclear. In this study, we identified that Tβ4 is significantly upregulated in breast cancer tissues and cell lines, and its high expression correlates with poor clinical outcomes. Functionally, Tβ4 promotes breast cancer cell proliferation, migration, epithelial–mesenchymal transition (EMT), and angiogenesis while inhibiting apoptosis. Mechanistically, Tβ4 directly regulates the expression of SLC7A11, a key cystine/glutamate antiporter, thereby enhancing glutathione biosynthesis and suppressing lipid peroxidation to inhibit ferroptosis. Rescue experiments further demonstrated that silencing SLC7A11 abrogates the oncogenic effects of Tβ4 both in vitro and in vivo. Collectively, these findings uncover a novel Tβ4/SLC7A11 axis that modulates ferroptosis sensitivity and contributes to breast cancer malignancy, offering potential therapeutic implications for targeting ferroptosis resistance.

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t - β4/SLC7A11信号通路调控乳腺癌进化的机制研究

胸腺素β4 （t - β4）在乳腺癌进展中起关键作用，但其分子机制尚不清楚。在本研究中，我们发现Tβ4在乳腺癌组织和细胞系中显著上调，其高表达与临床预后差相关。在功能上，Tβ4促进乳腺癌细胞增殖、迁移、上皮-间质转化（EMT）和血管生成，同时抑制细胞凋亡。机制上，t - β4直接调控关键的胱氨酸/谷氨酸反转运蛋白SLC7A11的表达，从而促进谷胱甘肽的生物合成，抑制脂质过氧化作用，抑制铁凋亡。挽救实验进一步证明，沉默SLC7A11在体外和体内均可消除t - β4的致癌作用。总之，这些发现揭示了一种新的Tβ4/SLC7A11轴，它调节铁下垂敏感性并参与乳腺癌恶性肿瘤，为靶向铁下垂耐药性提供了潜在的治疗意义。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.