Research Paper Volume 13, Issue 4 pp 5858—5874
GABARAP suppresses EMT and breast cancer progression via the AKT/mTOR signaling pathway
- 1 The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China
- 2 Radiology Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China
- 3 Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang 157000, China
Received: May 15, 2020 Accepted: November 20, 2020 Published: February 11, 2021https://doi.org/10.18632/aging.202510
How to Cite
Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Few studies have focused on γ-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 p-mTOR 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.
GABARAP: γ-aminobutyric acid type A (GABAA) receptor-associated protein(GABARAP); EMT: epithelial-mesenchymal transition(EMT); IHC: immunohistochemistry (IHC); MMP: matrix metalloproteinase (MMP); PRIP: p130/phospholipase C-related inactive protein (PRIP); AT1: angiotensin II type 1 (AT1); IDC: invasive ductal breast cancer (IDC); DCIS: ductal carcinoma in situ (DCIS); FFPE: Formalin-fixed paraffin-embedded (FFPE); TCGA: The Cancer Genome Atlas; LNM: lymph node metastasis(LNM); OS: overall survival; OD: optical density.