Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway.

// Lihong Bai 1, * , Gengpeng Lin 1, * , Longhua Sun 1, 2, * , Yangli Liu 1 , Xinyan Huang 1 , Chuangjie Cao 3 , Yubiao Guo 1 , Canmao Xie 1 1 Respiratory Department, The First Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China 2 Respiratory Department, Nanchang Hospital of Integrative Traditional Chinese and Western Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People's Republic of China 3 Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China * These authors contributed equally to this work Correspondence to: Canmao Xie, email: longfenghh@sina.cn Yubiao Guo, email: guoyubiao@hotmail.com Keywords: non-small cell lung cancer, ERK1/2, MMP9, SIRT6, biomarker Received: November 10, 2015      Accepted: May 20, 2016      Published: May 31, 2016 ABSTRACT Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer. Here, we report that elevated SIRT6 expression was correlated with clinicopathological parameters such as T and N classification in non-small cell lung cancer (NSCLC) patient tumors. SIRT6 overexpression in NSCLC cell lines increased extracellular signal-regulated kinase (p-ERK)1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. Upon treatment with a specific mitogen-activated protein kinase (MEK) 1/2 inhibitor, these effects were abolished. Our results demonstrate SIRT6 upregulation in NSCLC for the first time and suggest a functional role for SIRT6 in promoting migration and invasion through ERK1/2/MMP9 signaling. SIRT6 may serve as a potential therapeutic target in NSCLC and its utility as a prognostic indicator warrants further study.