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

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.