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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
JournalThe Journal of Pathology
Volume264
Issue number1
DOIs
StatePublished - Sep 1 2024

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