Usp8 promotes tumor cell migration through activating the JNK pathway |
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| Authors: | Yunhe Zhao Dezhen Peng Yanyun Liu Qian Zhang Bin Liu Yanran Deng Wenhao Ding Zizhang Zhou Qingxin Liu |
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| Affiliation: | 1.State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018 Tai’an, China ;2.Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 210009 Nanjing, China |
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| Abstract: | Tumor metastasis is the most cause of high mortality for cancer patients. Identification of novel factors that modulate tumor cell migration is of great significance for therapeutic strategies. Here, we find that the ubiquitin-specific protease 8 (Usp8) promotes tumor cell migration through activating the c-Jun N-terminal kinase (JNK) pathway. Genetic epistasis analyses uncover Usp8 acts upstream of Tak1 to control the JNK pathway. Consistently, biochemical results reveal that Usp8 binds Tak1 to remove ubiquitin modification from Tak1, leading to its stabilization. In addition, human USP8 also triggers tumor cell migration and activates the JNK pathway. Finally, we show that knockdown of USP8 in human breast cancer cells suppresses cell migration. Taken together, our findings demonstrate that a conserved Usp8-Tak1-JNK axis promotes tumor cell migration, and providing USP8 as a potential therapeutic target for cancer treatment.Subject terms: Metastasis, Cell migration |
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