Recently, the team of Prof. Qingxin Liu and Prof. Zizhang Zhou from the College of Life Sciences, Shandong Agricultural University (SDAU) published a research paper online in the academic journal Cell Death & Disease, revealing the regulation mechanism of tumor cell migration, which provides a potential therapeutic target for breast cancer treatment.

Screenshot of the paper

Cancer has become the leading cause of human death worldwide. Tumor metastasis, rather than the primary tumor overgrowth, is the main cause of tumor-induced mortality. Tumor metastasis is a complex process controlled by various genes, and its underlying mechanism still remains unclear.

 “Flies (Drosophila melanogaster) is currently used in biology research one of the most common pattern, previous studies have shown that Drosophila and mammalian genes and signal pathways have highly conservative, the researchers used Drosophila genetics techniques to simulate the process of human cancer.” Prof. Qingxin Liu told reporters.

During the study, Liu’s team observed that overexpression of the ubiquitin-specific protease 8 (Usp8) promotes tumor cell migration through activating the c-Jun N-terminal kinase (JNK) pathway. Compared with Usp8 alone, blocking JNK signalling effectively inhibited the enhanced tumor cell migration induced by Usp8 expression.

Ectopic expression of Usp8 induces cell migration

Co-immunoprecipitation (Co-IP) and GST pull down assay 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, Transwell assays shows that knockdown of Usp8 in human breast cancer cells suppresses cell migration.

A proposed model of Usp8 activating the JNK signaling and cell migration.

According to Prof. Zizhang Zhou, this research uncovers a conserved Usp8-Tak1-JNK axis to promote tumor cell migration, and provides Usp8 as a potential therapeutic target for JNK-related cancers.

Prof. Qingxin Liu and Prof. Zizhang Zhou are the co-corresponding authors. Dr. Yunhe Zhao and Dr. Dezhen Peng are the co-first authors of this paper. This work was supported by grants from the National Natural Science Foundation of China, and the National Key Research and Development Program of China, and the Natural Science Foundation of Shandong Province, Project funded by China Postdoctoral Science Foundation, and the Construction Engineering Special Fund of “Taishan Scholars”.

Link to the paper: https://www.nature.com/articles/s41419-022-04749-1

Email of Prof. Qingxin Liu: liuqingxin@sdau.edu.cn