SIRT1 promotes formation of breast cancer through modulating Akt activity

Abstract

The silent information regulation factor 1 (sirtuin Type 1, SIRT1), as a kind of NAD+ dependent class III histone deacetylation enzyme, has been found to be involved in tumor proliferation, invasion, and metastasis. The roles of SIRTl in breast cancer is multifaceted depending on its substrate from upstream or downstream signaling pathway. In this study, we sought to make clear the regulating effects of SIRT1 in breast cancer cells, and to explore the underlying mechanisms through which SIRT1 regulates breast cancer. First, our results showed that SIRT1 was significantly up-regulated in breast cancer tissues and cells, which correlated with histological grade, tumor size, as well as lymph node metastasis. Then we established SIRT1-overexpressed and SIRT1- knockdown breast cancer cell lines to investigate the functions of SIRT1 in regulating colony formation, cell proliferation, cell cycle, cell apoptosis and migration. We found that overexpression of SIRT1 significantly promoted breast cancer growth both in vitro and in vivo, whereas knockdown of SIRT1 inhibited these phenotypes. Furthermore, SIRT1 was found to interact with Akt directly, consequently promoting the activity of Akt in breast cancer cells in vitro and positively correlating with expression of Akt, P-Akt, in breast cancer tissues in vivo. Down regulation the activity of Akt partially weakened the proliferative effect mediated by SIRT1. Taken together, our results demonstrated SIRT1's tumor promotion function and potential mechanisms in breast cancer, thus providing valuable therapeutic targets for breast cancer.

Associations of sirtuins with clinicopathological variables and prognosis in human ovarian cancer

“…As a consequence, the high mRNA expression levels of SIRT1 and SIRT4 were associated with an unfavorable prognosis in patients with OC. Similarly, previous studies have also verified the roles of the aforementioned two SIRTs in other carcinomas, such as lung cancer (30,31), breast cancer (32)(33)(34), gastric cancer (35,36), and prostate cancer (37). Specifically, Shin et al (30) reported that high SIRT1 expression was identified in non-small cell lung cancer, which was highly associated with drug resistance via the SIRT1-mitogen-activated protein kinase signaling pathway.…”

Retracted Article: Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway

“…13 However, it plays different roles in different cancers, and may act as a tumor promoter or tumor suppressor. 42 Previous evidence suggests that SIRT1 silencing contributes to tumor suppression in various cancers, such as breast cancer 43 and colon cancer. 44 Qu et al showed that SIRT1 promoted proliferation and inhibited apoptosis in glioma cells, thereby promoting glioma tumorigenesis.…”

The Roles of Sirtuin Family Proteins in Cancer Progression

“…SIRT1 also enhances the activity of PI3K/AKT due to their direct interaction. Regarding AKT depletion, however, the SIRT1-mediated proliferative effect is only partially decreased in breast cancer [35]. In addition, the transcriptional level of SIRT1 is interrelated with lymph node-positive metastatic breast cancer [117].…”