SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4.

ABSTRACT:

Background

Epithelial-to-mesenchymal transition (EMT) contributes to the invasion and metastasis of epithelial tumors. Sirtuin 6 (SIRT6), an NAD-dependent deacetylase, is known to promote metastasis of non-small cell lung cancer (NSCLC).

Methods

In this work, we determined the role of SIRT6 in the EMT of NSCLC cells and identified the key EMT-related genes involved in the oncogenic activity of SIRT6.

Results

We report that depletion of SIRT6 inhibits transforming growth factor-β1 (TGF-β1)-induced EMT in A549 and H1299 NSCLC cells, which is rescued by ectopic expression of SIRT6. Knockdown of SIRT6 leads to a reduction in Snail protein without affecting the mRNA level. Immunoprecipitation experiments demonstrate a physical association between SIRT6 and Snail. SIRT6 dea

SUBMITTER: Li Z 

PROVIDER: S-EPMC6303940 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature