GILT stabilizes cofilin to promote the metastasis of prostate cancer.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-01-16 DOI:10.1038/s41420-025-02288-0

Dunsheng Han, Zhiming Wu, Cong Zhang, Ziwei Wei, Fan Chao, Xuefeng Xie, Jinke Liu, Yufeng Song, Xiaoming Song, Dingchang Shao, Shiyu Wang, Guoxiong Xu, Gang Chen

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Abstract

Gamma-interferon-induced lysosomal thiol reductase (GILT), known for catalyzing disulfide bond reduction, is involved in various physiological processes. While the involvement of GILT in the development of various tumors has been demonstrated, the mechanisms underlying its regulation in prostate cancer (PCa) are not fully understood. In the present study, we confirmed that GILT was significantly upregulated in PCa and facilitated tumor metastasis. Mechanistically, GILT stabilized the cofilin protein by competitively binding to cofilin with Src family tyrosine kinase (SRC), inhibiting SRC-mediated tyrosine phosphorylation of cofilin, thereby suppressing the ubiquitination pathway degradation of cofilin. GILT overexpression stabilized and increased the protein level of cofilin in PCa cells and promoted the metastasis of PCa cells by accelerating actin dynamics through cofilin-mediated actin severing. Our findings reveal a novel mechanism of GILT in PCa and provide a new potential target for the diagnosis and treatment of PCa patients.

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GILT稳定cofilin促进前列腺癌转移。

γ -干扰素诱导的溶酶体硫醇还原酶（GILT）以催化二硫键还原而闻名，参与多种生理过程。虽然GILT参与各种肿瘤的发展已被证实，但其在前列腺癌（PCa）中的调节机制尚不完全清楚。在本研究中，我们证实了GILT在PCa中显著上调，促进了肿瘤转移。在机制上，GILT通过Src家族酪氨酸激酶（Src）与cofilin竞争性结合，抑制Src介导的cofilin酪氨酸磷酸化，从而抑制cofilin的泛素化途径降解，从而稳定了cofilin蛋白。GILT过表达稳定并提高了PCa细胞中cofilin的蛋白水平，并通过cofilin介导的肌动蛋白切断加速了肌动蛋白动力学，促进了PCa细胞的转移。我们的研究结果揭示了GILT在PCa中的新机制，为PCa患者的诊断和治疗提供了新的潜在靶点。

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.