Usp8 promotes tumor cell migration through activating the JNK pathway

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 activati...

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Bibliographic Details
Published in:Cell death & disease 2022-03, Vol.13 (3), p.286-286, Article 286
Main Authors: Zhao, Yunhe, Peng, Dezhen, Liu, Yanyun, Zhang, Qian, Liu, Bin, Deng, Yanran, Ding, Wenhao, Zhou, Zizhang, Liu, Qingxin
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomedical and Life Sciences
Breast cancer
c-Jun protein
Cancer
Cell adhesion & migration
Cell Biology
Cell Culture
Cell migration
Cell Movement
Endopeptidases - genetics
Endopeptidases - metabolism
Endosomal Sorting Complexes Required for Transport - metabolism
Epistasis
Genetic analysis
Humans
Immunology
JNK Mitogen-Activated Protein Kinases - metabolism
JNK protein
Kinases
Life Sciences
MAP Kinase Signaling System
Metastases
Neoplasms - genetics
TAK1 protein
Therapeutic targets
Transcription factors
Tumors
Ubiquitin
Ubiquitin - metabolism
Ubiquitin Thiolesterase - genetics
Ubiquitin Thiolesterase - metabolism
Ubiquitin-specific proteinase
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-022-04749-1