Deacetylation by SIRT6 increases the stability of GILZ to suppress NSCLC cell migration and invasion

Glucocorticoid-induced leucine zipper (GILZ) plays a role in cancer cell proliferation in several tumor types. However, in our present study, GILZ was demonstrated to be a metastasis regulator but not a proliferation regulator in non-small cell lung cancer (NSCLC). The overexpression of GILZ had no significant effect on the proliferation of NSCLC cells but inhibited their metastasis by targeting the epithelial-mesenchymal transition pathway. The deacetylase SIRT6, a key regulator of protein stability, can enhance the stability of the GILZ protein by mediating its deacetylation, which prevents ubiquitination and degradation. This process ultimately enhances the inhibitory effect of GILZ on the migration and invasion of NSCLC cells. Thus, GILZ may be a promising new therapeutic target for tumor metastasis. •GILZ inhibits NSCLC cell migration and invasion by regulating the EMT process.•SIRT6 mediates the deacetylation of GILZ protein in NSCLC.•SIRT6-mediated deacetylation inhibits the degradation of GILZ.•GILZ is a potential therapeutic target for NSCLC tumor metastasis.