J Cancer 2018; 9(11):2012-2023. doi:10.7150/jca.24275

Research Paper

SIRT1 promotes formation of breast cancer through modulating Akt activity

Xiaoxia Jin1,2#, Yingze Wei1,2#, Feng Xu3, Min Zhao2, Kui Dai2, Rong Shen2, Shuyun Yang2✉, Nong Zhang1✉

1. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China
2. Department of Pathology, Nantong Tumor Hospital, Nantong, Jiangsu, China
3. Department of Thoracic Surgery, Nantong Tumor Hospital, Nantong, Jiangsu, China
# Both authors contributed equally to this study.

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.

Keywords: SIRT1, Akt, cell proliferation, Breast cancer

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How to cite this article:
Jin X, Wei Y, Xu F, Zhao M, Dai K, Shen R, Yang S, Zhang N. SIRT1 promotes formation of breast cancer through modulating Akt activity. J Cancer 2018; 9(11):2012-2023. doi:10.7150/jca.24275. Available from http://www.jcancer.org/v09p2012.htm