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Usp8 promotes tumor cell migration through activating the JNK pathway
Yunhe Zhao1, Dezhen Peng2, Yanyun Liu1
1State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.
Cell Death & Disease
|April 1, 2022
Summary
The ubiquitin-specific protease 8 (Usp8) drives cancer cell migration by activating the JNK pathway. Targeting Usp8 may offer a new therapeutic strategy for treating cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor metastasis is a primary driver of cancer mortality.
- Identifying factors that regulate cancer cell migration is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of ubiquitin-specific protease 8 (Usp8) in tumor cell migration.
- To elucidate the molecular mechanism by which Usp8 influences cancer cell motility.
Main Methods:
- Genetic epistasis analyses were performed to determine the position of Usp8 within signaling pathways.
- Biochemical assays were used to examine the interaction between Usp8 and Tak1.
- Experiments involving knockdown of USP8 in human breast cancer cells were conducted.
Main Results:
- Usp8 was found to promote tumor cell migration by activating the c-Jun N-terminal kinase (JNK) pathway.
- Usp8 acts upstream of Tak1 to regulate the JNK pathway.
- Usp8 binds to Tak1, removes ubiquitin modifications, and stabilizes Tak1, thereby enhancing JNK pathway activation. Human USP8 also promotes migration and JNK activation.
- Knockdown of USP8 significantly suppressed migration in human breast cancer cells.
Conclusions:
- A conserved Usp8-Tak1-JNK signaling axis promotes tumor cell migration.
- USP8 represents a potential therapeutic target for inhibiting cancer metastasis.
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