Research Paper Volume 13, Issue 3 pp 3886—3897
Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways
- 1 Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- 2 Laboratory of Functional Materials, Henan University of Technology, Henan Province, China
- 3 Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
- 4 Department of Surgery, The Infectious Disease Hospital of Heilongjiang Province, Harbin, Heilongjiang Province, China
Received: June 24, 2020 Accepted: September 29, 2020 Published: January 10, 2021
https://doi.org/10.18632/aging.202356How to Cite
Copyright: © 2021 Zhao 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
Gastric cancer (GC) is a common malignant tumor, which has a high incidence and fatality. Therefore, it is important to clarify the molecular mechanism of the occurrence and development for GC and to find more effective treatments and targeted drugs. In this study, we found that the kinase suppressor of Ras1 (KSR1) was increased in GC tissues and cell lines. Silencing of KSR1 inhibited the proliferation, migration and invasion of MKN-45 cells. E3 ligase Praja2 was downregulated in GC tissues and cell lines. In addition, praja2 promoted ubiquitylation of KSR1, but inhibited MEK-ERK signal pathways. Functional analysis indicated overexpression of praja2 inhibited the proliferation, migration and invasion of MKN-45 cells, while MG132 or FGF2 treatment removed the inhibitory effects of praja2 on GC progression. In vivo tumorigenesis experiments indicated praja2 inhibited tumor growth via KSR1-MEK-ERK axis. In conclusion, praja2 promoted the ubiquitylation and degradation of KSR1, which disturbed MEK- ERK signaling and inhibited GC progression. Our study might provide a novel target for GC clinical treatment.