G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin

Cong-hui Zhang1, Hong Liu1, Wu-li Zhao1, Wen-xia Zhao1, Hui-min Zhou1, Rong-guang Shao1
1 Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China
Correspondence to: Rong-guang Shao:,
DOI: 10.1038/s41401-020-00598-w
Received: 9 August 2020
Accepted: 13 December 2020
Advance online: 3 February 2021


Ras-GTPase activating SH3 domain-binding protein 1 (G3BP1) is a multifunctional binding protein involved in the development of a variety of human cancers. However, the role of G3BP1 in breast cancer progression remains largely unknown. In this study, we report that G3BP1 is upregulated and correlated with poor prognosis in breast cancer. Overexpression of G3BP1 promotes breast cancer cell proliferation by stimulating β-catenin signaling, which upregulates a number of proliferation-related genes. We further show that G3BP1 improves the stability of β-catenin by inhibiting its ubiquitin-proteasome degradation rather than affecting the transcription of β-catenin. Mechanistically, elevated G3BP1 interacts with and inactivates GSK-3β to suppress β-catenin phosphorylation and degradation. Disturbing the G3BP1-GSK-3β interaction accelerates the degradation of β-catenin, impairing the proliferative capacity of breast cancer cells. Our study demonstrates that the regulatory mechanism of the G3BP1/GSK-3β/β-catenin axis may be a potential therapeutic target for breast cancer.
Keywords: G3BP1; Wnt/β-catenin signaling pathway; GSK-3β phosphorylation; protein stability; breast cancer; peptide antagonist

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