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Research Paper|Volume 13, Issue 4|pp 5858—5874

GABARAP suppresses EMT and breast cancer progression via the AKT/mTOR signaling pathway

Ying Liu1, Dandan Wang1, Mengxia Lei1, Jiayi Gao1, Yuqing Cui1, Xiaoying Jin1, Qiujie Yu2, Ying Jiang3, Yan Guo1, Yali Liu1, Li Cai1, Xuesong Chen1
  • 1The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China
  • 2Radiology Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China
  • 3Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang 157000, China
Received: May 15, 2020Accepted: November 20, 2020Published: February 11, 2021
https://doi.org/10.18632/aging.202510

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.

Abstract

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.