SIRT1 contributes to neuroendocrine differentiation of prostate cancer.

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

doi:10.18632/oncotarget.23111

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.

Highlights

Prostate cancer (Pca) is the most common cancer among men and the second leading cause of death from cancer in the US [1]
In the dataset of neuroendocrine Pca published by Trento in 2016 [18], SIRT1 amplification was found in 19% of 77 cases
In a metastatic Pca dataset published by Robinson et al in 2015 [19], SIRT1 amplification was identified in 9% of 150 cases (Figure 1A)

Summary

Introduction

Prostate cancer (Pca) is the most common cancer among men and the second leading cause of death from cancer in the US [1]. Most patients with clinically localized Pca receive curative treatments, including radical prostatectomy or radiotherapy. Between 20% and 40% of these patients eventually experience biochemical recurrence [2]. These patients receive androgen deprivation therapy (ADT). ADT can prolong patients’ overall survival and decrease their tumor burden, all patients eventually become resistant to ADT, developing a condition called castration-resistant Pca (CRPC) [3]. A previous study reported that CRPC, as shown by disease progression, will develop after 12-18 months of ADT [4]

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Conclusion