Research Paper Volume 11, Issue 22 pp 10697—10710
MAP2K4 interacts with Vimentin to activate the PI3K/AKT pathway and promotes breast cancer pathogenesis
- 1 Southern Medical University, Nanfang Hospital, Department of Oncology, Guangzhou 510515, Guangdong, P. R. China
- 2 Guizhou Maternity and Child Health Hospital, Guiyang 550003, Guizhou, P. R. China
- 3 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510310, Guangdong, P. R. China
- 4 Department of General Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550001, Guizhou, P. R. China
received: August 22, 2019 ; accepted: November 8, 2019 ; published: November 25, 2019 ;https://doi.org/10.18632/aging.102485
How to Cite
Copyright © 2019 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.
Mitogen-activated protein kinase kinase 4 (MAP2K4) is a member of the mitogen-activated protein kinase (MAPK) activator family. MAPK signaling plays a significant role in cell proliferation, differentiation, transcriptional regulation, and development. However, specific function and mechanism of MAP2K4 in breast cancer have not been clarified. According to our study, overexpressed MAP2K4 in breast cancer cells increased proliferation, migration, and invasion in vivo and in vitro, while MAP2K4 knockdown restored the effects. Subsequent mechanistic analyses demonstrated that MAP2K4 promoted cell proliferation, migration, and invasion by activating phosphoinositide-3-kinase (PI3K)/AKT signaling, the downstream proteins, c-JUN, the G1/S cell cycle, and the epithelial-to-mesenchymal transition (EMT). Meanwhile, MAP2K4 interacted with Vimentin and further propagated the malignant phenotype. Furthermore, patients with high MAP2K4 and Vimentin expression levels had poorer overall survival rates than those with low expression levels of both proteins. Our studies demonstrated that MAP2K4 has the potential to serve as an oncogene in breast cancer and it activates the phosphorylated PI3K/AKT signaling pathway to activate downstream cycle-associated proteins and EMT signals while interacting with Vimentin to promote breast cancer cells proliferation, migration, and invasion. In our study, MAP2K4 and Vimentin co-expression is confirmed to be an unfavorable factor in breast cancer.