Open Access
ARTICLE
GSK-3b Promotes Cell Migration and Inhibits Autophagy by Mediating the AMPK Pathway in Breast Cancer
Lu Guo*, Duankai Chen†, Xing Yin‡, Qingfeng Shu†
* Jinan University, Guangzhou, Guangdong, P.R. China
† General Surgery, YouJiang Medical University for Nationalities, Guangxi, P.R. China
‡ Wound Regeneration and Vascular Surgery Department of the First Affiliated Hospital of Guangxi
University of Chinese Medicine, Guangxi, P.R. China
Oncology Research 2019, 27(4), 487-494. https://doi.org/10.3727/096504018X15323394008784
Abstract
GSK-3 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-3 to predict clinical outcome in
BC patients. GSK-3 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-3 expression in BC tissues, which was correlated with worse clinicopathological parameters and clinical outcome.
Progression of BC was suppressed by GSK-3 knockdown. Furthermore, suppression of GSK-3 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-3 function, in parallel with increased generation of LC3 II. Our findings
therefore indicate that GSK-3 participates in regulation of migration as well as stimulation of autophagy
via mediating activation of the AMPK pathway. This suggests that GSK-3 has potential as a predictor of
clinical outcome and as a target for BC therapy.
Cite This Article
Guo, L., Chen, D., Yin, X., Shu, Q. (2019). GSK-3b Promotes Cell Migration and Inhibits Autophagy by Mediating the AMPK Pathway in Breast Cancer.
Oncology Research, 27(4), 487–494. https://doi.org/10.3727/096504018X15323394008784