Phosphorylation of SIK1 by Akt1 activates STAT3 signal pathway in breast cancer cell.

As a member of AMPK-related kinases, salt-inducible kinase 1 (SIK1) regulates energy response-related physiopathological processes, such as gluconeogenesis and lipid metabolism. More recently, instead of AMPK, SIK1 has been strikingly defined as a major player for tumor suppressor liver kinase 1 (LKB1) deficient NSCLC. However, the exact roles and upstream regulators of SIK1 in breast cancer are not well defined.We found that Akt1 can directly phosphorylate SIK1 and inhibit the kinase activity of SIK1, promoting the progress of breast cancer. To investigate the mechanism of Akt1 phosphorylated SIK1 promoting the progression of breast cancer, we constructed a stable expression of SIK1 WT and S435D in BT549, and then performed gene expression profiling analysis. Overall design: Comparative gene expression profiling analysis of RNA-seq data for BT549 Overexpressing SIK1 WT and S435D.