RETRACTED ARTICLE: SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4
KLF4
Ectopic expression
DOI:
10.1186/s13046-018-0984-z
Publication Date:
2018-12-22T01:43:42Z
AUTHORS (7)
ABSTRACT
Epithelial-to-mesenchymal transition (EMT) contributes to the invasion and metastasis of epithelial tumors. Sirtuin 6 (SIRT6), an NAD-dependent deacetylase, is known promote non-small cell lung cancer (NSCLC).In this work, we determined role SIRT6 in EMT NSCLC cells identified key EMT-related genes involved oncogenic activity SIRT6.We report that depletion inhibits transforming growth factor-β1 (TGF-β1)-induced A549 H1299 cells, which rescued by ectopic expression SIRT6. Knockdown leads a reduction Snail protein without affecting mRNA level. Immunoprecipitation experiments demonstrate physical association between Snail. deacetylates prevents its proteasomal degradation. Silencing blunts SIRT6-induced migration invasion, while overexpression restores SIRT6-depleted cells. upregulation kruppel-like factor 4 (KLF4) reduced binding promoter Klf4 KLF4 rescues invasive capacity Conversely, co-expression impairs aggressive behavior. In vivo data further antagonized KLF4.These findings provide mechanistic insights into pro-metastatic highlight SIRT6/Snail/KLF4 axis regulating
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