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Research Paper|Volume 14, Issue 13|pp 5493—5510

E3 ubiquitin ligase RBX1 drives the metastasis of triple negative breast cancer through a FBXO45-TWIST1-dependent degradation mechanism

Jun Shao1, Qian Feng1, Weifan Jiang4, Yuting Yang5, Zhiqiang Liu6, Liang Li7, Wenlong Yang3, Yufeng Zou2,5
  • 1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
  • 2Department of Breast Surgery, The Third Hospital of Nanchang, Jiangxi Provincial-Key-Laboratory for Breast Diseases, Nanchang 330006, Jiangxi Province, China
  • 3Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
  • 4Department of Urology Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
  • 5Department of Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • 6Department of Neurology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, Jiangxi Province, China
  • 7Emergency Department, Jiangxi Maternal and Child Health Hospital, Nanchang 330006, Jiangxi Province, China
* Equal contribution
Received: March 1, 2022Accepted: June 23, 2022Published: July 8, 2022
https://doi.org/10.18632/aging.204163

Copyright: © 2022 Shao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Triple-negative breast cancer (TNBC) patients are at high risk of recurrence and metastasis in the early stages, although receiving standard treatment. However, the underlying mechanism of TNBC remains unclear. Here, the critical effect of E3 ubiquitin ligase RBX1 in the metastasis of TNBC was reported for the first time. We discovered that RBX1 expression was evidently raised in the tissues of TNBC. Our clinical research displayed that high RBX1 expression was markedly related to poor distant invasion and survival. Functional analysis exhibited that RBX1 facilitated metastasis of TNBC cells through increasing EMT. Furthermore, we demonstrated that RBX1 knockdown increased the levels of the Twist family bHLH transcription factor 1 (TWIST1), is a significant regulator in the EMT process in some cancers. It can be observed an evident positive correlation between the TWIST1 and RBX1 levels, further confirming that EMT induced by RBX1 in TNBC cells is determined by TWIST1. Mechanistically, RBX1 modulates the expression of TWIST1 via modulating FBXO45, directly binding to FBXO45, and facilitating its degradation and ubiquitination. Briefly, our findings confirm that RBX1 is probably a new biomarker of TNBC carcinogenesis, thus suggesting that targeting the RBX1/FBXO45/TWIST1 axis may be an underlying strategy for TNBC treatment.