Open AccessSIRT1 contributes to neuroendocrine differentiation of prostate cancer
Author(s) -
Linhui Ruan,
Lei Wang,
Xiaosong Wang,
Ming He,
Xiaoguang Yao
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.23111
Subject(s) - neuroendocrine differentiation , prostate cancer , cancer research , androgen deprivation therapy , protein kinase b , pi3k/akt/mtor pathway , prostate , medicine , cancer , androgen , epigenetics , endocrinology , biology , signal transduction , microbiology and biotechnology , hormone , biochemistry , gene
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.