Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer

Yuning Liao†,
Zhiqiang Guo†,
Xiaohong Xia†,
Yuan Liu,
Chuyi Huang,
Lili Jiang,
Xuejun Wang,
Jinbao LiuEmail author and
Hongbiao HuangEmail author

†Contributed equally

Journal of Experimental & Clinical Cancer Research201938:157

https://doi.org/10.1186/s13046-019-1165-4

Received: 23 November 2018
Accepted: 2 April 2019
Published: 11 April 2019

Abstract

Background

Prostate cancer (PCa) remains a challenge worldwide. Due to the development of castration-resistance, traditional first-line androgen deprivation therapy (ADT) became powerlessness. Epidermal growth factor receptor (EGFR) is a well characterized therapeutic target to treat colorectal carcinoma and non-small cell lung cancer. Increasing studies have unraveled the significance of EGFR and its downstream signaling in the progression of castration-resistant PCa.

Method

MTS, colony formation and Edu staining assays were used to analyze the cell proliferation of PCa cells. Flow cytometry was used to analyze PCa cell cycle distribution and cell apoptosis. Western blot was used to measure the expression of key proteins associated with cell cycle progression, apoptosis and EGFR signaling pathways. Transfection of exogenous small interfering RNA (siRNA) or plasmid was used to intervene specific gene expression. Nude mouse model was employed to test the in vivo effect of Spautin-1.

Results

The current study reveals that Spautin-1, a known inhibitor of ubiquitin-specific peptidase 10 (USP10) and USP13, inhibits EGFR phosphorylation and the activation of its downstream signaling. Inhibition of EGFR signaling induced by Spautin-1 leads to cell cycle arrest and apoptosis of PCa in a USP10/USP13 independent manner. The application of Spautin-1 reduces the expression of glucose transporter 1 (Glut1) and dramatically induces cell death under glucose deprivation condition. In vivo experiments show a potent anti-tumor effect of Spautin-1 alone and in combination with Enzalutamide.