Histone demethylase PHF8 promotes prostate cancer metastasis via the E2F1–SNAI1 axis

IF 5.6 2区医学 Q1 ONCOLOGY The Journal of Pathology Pub Date : 2024-07-18 DOI:10.1002/path.6325

Ze Wang, Peng Tang, Haiyang Xiao, Song Peng, Jian Chen, Yapeng Wang, Jing Xu, Qian Yan, Junying Zhang, Jie Deng, Qiang Ma, Hailin Zhu, Weiming Luo, Dianzheng Zhang, Luofu Wang, Jun Qin, Weihua Lan, Jun Jiang, Qiuli Liu

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Abstract

Metastasis is the primary culprit behind cancer-related fatalities in multiple cancer types, including prostate cancer. Despite great advances, the precise mechanisms underlying prostate cancer metastasis are far from complete. By using a transgenic mouse prostate cancer model (TRAMP) with and without Phf8 knockout, we have identified a crucial role of PHF8 in prostate cancer metastasis. By complexing with E2F1, PHF8 transcriptionally upregulates SNAI1 in a demethylation-dependent manner. The upregulated SNAI1 subsequently enhances epithelial-to-mesenchymal transition (EMT) and metastasis. Given the role of the abnormally activated PHF8/E2F1-SNAI1 axis in prostate cancer metastasis and poor prognosis, the levels of PHF8 or the activity of this axis could serve as biomarkers for prostate cancer metastasis. Moreover, targeting this axis could become a potential therapeutic strategy for prostate cancer treatment. © 2024 The Pathological Society of Great Britain and Ireland.

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组蛋白去甲基化酶PHF8通过E2F1-SNAI1轴促进前列腺癌转移

转移是导致包括前列腺癌在内的多种癌症死亡的罪魁祸首。尽管取得了很大进展，但前列腺癌转移的确切机制还远未完全阐明。通过使用Phf8基因敲除和未敲除的转基因小鼠前列腺癌模型（TRAMP），我们发现了PHF8在前列腺癌转移中的关键作用。通过与 E2F1 复合物，PHF8 以去甲基化依赖的方式转录上调 SNAI1。上调的 SNAI1 随后会促进上皮细胞向间质转化（EMT）和转移。鉴于异常激活的 PHF8/E2F1-SNAI1 轴在前列腺癌转移和不良预后中的作用，PHF8 的水平或该轴的活性可作为前列腺癌转移的生物标志物。此外，以该轴为靶点可能成为治疗前列腺癌的一种潜在策略。© 2024 大不列颠及爱尔兰病理学会。

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.