Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway
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Lihong Bai1,*, Gengpeng Lin1,*, Longhua Sun1,2,*, Yangli Liu1, Xinyan Huang1, Chuangjie Cao3, Yubiao Guo1, Canmao Xie1
1Respiratory 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
2Respiratory Department, Nanchang Hospital of Integrative Traditional Chinese and Western Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People's Republic of China
3Department 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
Canmao Xie, email: [email protected]
Yubiao Guo, email: [email protected]
Keywords: non-small cell lung cancer, ERK1/2, MMP9, SIRT6, biomarker
Received: November 10, 2015 Accepted: May 20, 2016 Published: May 31, 2016
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.
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