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 Liu, Hongbiao Huang

Research output: Contribution to journalArticle

1 Citation (Scopus)

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. Conclusion: This study demonstrates the therapeutic potential of EGFR signaling inhibition by the use of Spautin-1 for PCa treatment.

Original languageEnglish (US)
Article number157
JournalJournal of Experimental and Clinical Cancer Research
Volume38
Issue number1
DOIs
StatePublished - Apr 11 2019

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Epidermal Growth Factor Receptor
Prostatic Neoplasms
Castration
Apoptosis
Ubiquitin
Cell Cycle
Peptide Hydrolases
Therapeutics
Facilitative Glucose Transport Proteins
Cell Cycle Checkpoints
Nude Mice
Non-Small Cell Lung Carcinoma
Small Interfering RNA
Androgens
Transfection
spautin-1
Colorectal Neoplasms
Flow Cytometry
Plasmids
Cell Death

Keywords

  • Apoptosis
  • EGFR
  • Glut1
  • Prostate cancer
  • Spautin-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer. / Liao, Yuning; Guo, Zhiqiang; Xia, Xiaohong; Liu, Yuan; Huang, Chuyi; Jiang, Lili; Wang, Xuejun; Liu, Jinbao; Huang, Hongbiao.

In: Journal of Experimental and Clinical Cancer Research, Vol. 38, No. 1, 157, 11.04.2019.

Research output: Contribution to journalArticle

Liao, Yuning ; Guo, Zhiqiang ; Xia, Xiaohong ; Liu, Yuan ; Huang, Chuyi ; Jiang, Lili ; Wang, Xuejun ; Liu, Jinbao ; Huang, Hongbiao. / Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer. In: Journal of Experimental and Clinical Cancer Research. 2019 ; Vol. 38, No. 1.
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AB - 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. Conclusion: This study demonstrates the therapeutic potential of EGFR signaling inhibition by the use of Spautin-1 for PCa treatment.

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