https://doi.org/10.4081/ejh.2021.3214

Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1

Vol. 65 No. 1 (2021)
Submitted: 28 December 2020
Accepted: 2 February 2021
Published: 10 March 2021
TRIM6, STUB1, ubiquitination, breast cancer, growth, migration
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Authors

Chuanchao Wei
Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Jiayue Wu
Department of Special Ward One, Shanghai Pulmonary Hospital, Shanghai, China.
Weiyan Liu
Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Jingfeng Lu
Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Hongchang Li
Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.
Benjun Hai
licchong1@163.com
https://orcid.org/0000-0002-9970-7692
Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.

Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.

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Ethics Approval

All procedures performed in this study involving human participants were in accordance with the standards upheld by the Ethics Committee of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University and with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects. All animal experiments were approved by the Ethics Committee of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines

Supporting Agencies

This work was supported by the National Natural Science Foundation of China (NSFC)

How to Cite

Wei, C. ., Wu, J. ., Liu, W., Lu, J. ., Li, H. ., & Hai, B. (2021). Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3214

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