期刊
AGING-US
卷 13, 期 4, 页码 5858-5874出版社
IMPACT JOURNALS LLC
关键词
GABARAP; breast cancer; EMT; prognosis; AKT/mTOR pathway
资金
- National Natural Science Foundation of China [81773295, 81573001]
This study revealed the inhibitory effect of GABARAP on malignant behaviors in breast cancer through the AKT/mTOR pathway. Low levels of GABARAP were associated with advanced clinicopathological features and poor prognosis of breast cancer patients.
Few studies have focused on gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) in tumor progression. We investigated the expression and importance of GABARAP in breast cancer. We analyzed the expression of GABARAP and its relationship with clinicopathological features and prognosis (TCGA). To explain the role and potential mechanism of GABARAP in regulating tumor development, we performed acquisition and loss of function experiments using cell lines and models of mouse xenotransplantation. We found that GABARAP inhibited proliferation, migration and invasion in vitro and in vivo. Notably, low levels of GABARAP induced the epithelial-mesenchymal transition (EMT). Low levels of GABARAP increased p-AKT and pmTOR levels, and a specific AKT pathway inhibitor reversed the downregulation of GABARAP-induced tumor progression. GABARAP negatively correlated with advanced clinicopathological features in clinical specimens, such as tumor size and TNM stage. Notably, patients with low GABARAP levels had a poor prognosis. Immunohistochemistry (IHC) revealed that GABARAP expression negatively correlated with matrix metalloproteinase (MMP) 2 and MMP14. Conclusively, these data indicate that GABARAP suppresses the malignant behaviors of breast cancer likely via the AKT/mTOR pathway. The targeting of GABARAP may improve the certainty of diagnosis and treatment strategies for breast cancer.
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