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

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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SIRT6上调可预测不良预后并通过ERK1/2/MMP9通路促进非小细胞肺癌转移

DOI:
10.18632/oncotarget.9750
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发表时间:
2016-06-28
期刊:
影响因子:
--
通讯作者:
Xie C
Xie C
中科院分区:
其他
文献类型:
--
作者:
Bai L;Lin G;Sun L;Liu Y;Huang X;Cao C;Guo Y;Xie C

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Sirtuin 6(SIRT 6)是sirtuins蛋白家族的成员,在癌症中起着多种复杂的作用。在这里,我们报告了SIRT 6表达升高与非小细胞肺癌(NSCLC)患者肿瘤的T和N分类等临床病理参数相关。SIRT 6在NSCLC细胞系中的过表达增加了细胞外信号调节激酶(p-ERK)1/2磷酸化,激活了基质金属蛋白酶9(MMP 9),并促进了肿瘤细胞的迁移和侵袭。经特定的丝裂原活化蛋白激酶(MEK)1/2抑制剂治疗后,这些影响被取消。我们的研究结果首次证明了SIRT 6在NSCLC中的上调,并表明SIRT 6通过ERK 1/2/MMP 9信号在促进迁移和侵袭中的功能作用。SIRT 6可能作为NSCLC的潜在治疗靶点,其作为预后指标的实用性值得进一步研究。
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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