SIRT1 contributes to neuroendocrine differentiation of prostate cancer

Lin Ruan; Lei Wang; Xiaosong Wang; Ming He; Xiaoguang Yao

doi:10.18632/oncotarget.23111

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Research Papers:

SIRT1 contributes to neuroendocrine differentiation of prostate cancer

Lin Ruan, Lei Wang, Xiaosong Wang, Ming He and Xiaoguang Yao _

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Oncotarget. 2018; 9:2002-2016. https://doi.org/10.18632/oncotarget.23111

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Abstract

Lin Ruan1,2,*, Lei Wang3,*, Xiaosong Wang1,4, Ming He1,4 and Xiaoguang Yao1,4

1Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China

2Department of Nephrology, The First Hospital of Hebei Medical University, Shijiazhuang, China

3Department of Urology, The First Hospital of Hebei Medical University, Shijiazhuang, China

4College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China

*These authors have contributed equally to this work

Correspondence to:

Xiaoguang Yao, email: [email protected]

Keywords: prostate cancer; SIRT1; neuroendocrine; N-Myc; Akt

Received: July 27, 2017 Accepted: November 11, 2017 Published: December 11, 2017

ABSTRACT

The epigenetic factor SIRT1 can promote prostate cancer progression, but it is unclear whether SIRT1 contributes to neuroendocrine differentiation. In this study, we showed that androgen deprivation can induce reactive oxygen species production and that reactive oxygen species, in turn, activate SIRT1 expression. The increased SIRT1 expression induces neuroendocrine differentiation of prostate cancer cells by activating the Akt pathway. In addition, the interaction between Akt and SIRT1 is independent of N-Myc and can drive the development of neuroendocrine prostate cancer when N-Myc is blocked. Furthermore, SIRT1 facilitates tumor maintenance, and targeting SIRT1 may reduce the tumor burden during androgen deprivation. Our findings suggest that SIRT1 is a potential target for therapeutic intervention.

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Research Papers:

SIRT1 contributes to neuroendocrine differentiation of prostate cancer

Abstract