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- Title
RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR.
- Authors
Wan, Xing; Song, Yongxi; Fang, Honghong; Xu, Ling; Che, Xiaofang; Wang, Shuo; Zhang, Xiaomeng; Zhang, Lingyun; Li, Ce; Fan, Yibo; Hou, Kezuo; Li, Zhi; Wang, Xueqing; Liu, Yunpeng; Qu, Xiujuan
- Abstract
publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2020 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2020 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 12 article‐registration‐date‐day 13 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_249.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> 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.
- Subjects
TRANCE protein; INTERNET pharmacies; CANCER cell migration; EPIDERMAL growth factor; TUMOR necrosis factors; EPIDERMAL growth factor receptors; CHEMERIN
- Publication
Clinical & Translational Medicine, 2020, Vol 9, Issue 1, p1
- ISSN
2001-1326
- Publication type
Article
- DOI
10.1186/s40169-019-0249-2