GSK-3β Promotes Cell Migration and Inhibits Autophagy by Mediating the AMPK Pathway in Breast Cancer.

GSK-3β is a versatile protein kinase participating in many reactions. Currently, there is insufficient understanding of its influence on breast cancer (BC). In order to explore its influence on migration and invasion in BC, we investigated its expression in BC cell lines using qRT-PCR and Western blot (WB). Immunohistochemistry (IHC) was used to examine the potential of GSK-3β to predict clinical outcome in BC patients. GSK-3β knockdown was achieved using an shRNA plasmid vector in T47D cells. Our research explored the biological reactions and downstream pathways involved. We found excessive GSK-3β expression in BC tissues, which was correlated with worse clinicopathological parameters and clinical outcome. Progression of BC was suppressed by GSK-3β knockdown. Furthermore, suppression of GSK-3β function led to a noticeable decrease in ATP generation, and this was associated with stimulation of AMP-activated protein kinase (AMPK) in T47D cells. Activation of AMPK, a typical sign of autophagy stimulation, was triggered after suppression of GSK-3β function, in parallel with increased generation of LC3 II. Our findings therefore indicate that GSK-3β participates in regulation of migration as well as stimulation of autophagy via mediating activation of the AMPK pathway. This suggests that GSK-3β has potential as a predictor of clinical outcome and as a target for BC therapy.