Int J Med Sci 2020; 17(17):2809-2818. doi:10.7150/ijms.50206 This issue
1. Department of Pathology, Xuzhou Medical University, Xuzhou, China.
2. Jiangsu Key Laboratory of New drug and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
3. School of Pharmacy, Xuzhou Medical University, Xuzhou, China.
4. Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
5. Department of Human Anatomy, Xuzhou Medical University, Xuzhou, China.
#These authors contributed equally to this work.
Background: CSN6, a subunit of the highly conserved constitutive photomorphogenesis 9 (COP9) signalosome (CSN), has been reported to be implicated in tumor progression in various kinds of malignant tumors. However, the mechanism underlying CSN6 in the tumor development of breast cancer has not yet been fully elucidated.
Methods: CSN6 staining in breast cancer tissues and paracancerous tissues was measured by tissue microarray (TMA) technology. The metastatic effect of CSN6 was measured by cell migration assay. Co-immunoprecipitation study was used to show the interaction between the protein CSN6 and Snail1. Ubiquitination assay was performed to validate whether ubiquitination is involved in the upregulation of Snail1 by CSN6. The impact of CSN6 on tumor metastasis in vivo was analyzed using xenotransplantation experiments in BALB/c mice.
Results: Here, we demonstrated that CSN6 expression was dramatically increased in breast cancer tissues compared with paired adjacent cancerous tissues. CSN6 promoted the cell migration and wound healing abilities in breast cancer cell lines. Also we showed that CSN6 associates with Snail1 and enhances Snail1 protein level by inhibiting the ubiquitin-mediated degradation of Snail1. Thus, CSN6 is involved in positively regulating the stability of Snail1. We further proved that CSN6 protein level was positively correlated with the Snail1 expression in xenograft model.
Conclusion: These findings provide new insight into applicability of using the CSN6-Snail1 axis as a potential therapeutic target in breast cancer.
Keywords: CSN6, Snail1, cell migration, breast cancer