Document Type
Journal Article
Publication Title
Clinical and translational medicine
Volume
9
Issue
1
First Page
3
PubMed ID
31933009
Publisher
Springer
School
School of Medical and Health Sciences
Abstract
BACKGROUND: The incidence and mortality rates of gastric cancer (GC) rank in top five among all malignant tumors. Chemokines and their receptor-signaling pathways reportedly play key roles in the metastasis of malignant tumor cells. Receptor activator of nuclear factor κB ligand (RANKL) is a member of the tumor necrosis factor family, with strong chemokine-like effects. Some studies have pointed out that the RANKL/RANK pathway is vital for the metastasis of cancer cells, but the specific mechanisms in GC remain poorly understood. RESULTS: This study reports original findings in cell culture models and in patients with GC. Flow cytometry and western blotting analyses showed that RANK was expressed in BGC-823 and SGC-7901 cells in particular. Chemotaxis experiments and wound healing assay suggested that RANKL spurred the migration of GC cells. This effect was offset by osteoprotegerin (OPG), a decoy receptor for RANKL. RANKL contributed to the activation of human epidermal growth factor receptor (HER) family pathways. The lipid raft core protein, caveolin 1 (Cav-1), interacted with both RANK and human epidermal growth factor receptor-1(EGFR). Knockdown of Cav-1 blocked the activation of EGFR and cell migration induced by RANKL. Moreover, RANK-positive GC patients who displayed higher levels of EGFR expression had poor overall survival. CONCLUSIONS: In summary, we confirmed that with the promotion of RANKL, RANK and EGFR can form complexes with the lipid raft core protein Cav-1, which together promote GC cell migration. The formation of the RANK-Cav-1-EGFR complex provides a novel mechanism for the metastasis of GC. These observations warrant confirmation in independent studies, in vitro and in vivo. They also inform future drug target discovery research and innovation in the treatment of GC progression.
DOI
10.1186/s40169-019-0249-2
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Wan, X., Song, Y., Fang, H., Xu, L., Che, X., Wang, S., ... & Qu, X. (2020). RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR. Clinical and translational medicine, 9(1), 1-9. https://doi.org/10.1186/s40169-019-0249-2