AFAP1L1 promotes gastric cancer progression by interacting with VAV2 to facilitate CDC42-mediated activation of ITGA5 signaling pathway

被引:12
作者
Sun, Bo [1 ]
Ding, Bai [1 ]
Chen, Yu [1 ]
Peng, Chuang [1 ]
Chen, Xu [1 ]
机构
[1] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Hepatobiliary Surg, 61 Jiefang West Rd, Changsha 410005, Hunan, Peoples R China
关键词
Actin filament associated protein 1 like 1; Epithelial-mesenchymal transition; Gastric cancer; Integrin subunit alpha 5; ADAPTER PROTEIN; MIGRATION; GROWTH; CELLS; IDENTIFICATION; CYTOSKELETON; CONTRIBUTES; AFAP-110; INVASION; XB130;
D O I
10.1186/s12967-023-03871-8
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background The actin filament-associated protein (AFAP) family genes include AFAP1/AFAP-110, AFAP1L1 and AFAP1L2/XB130. Increasing evidence indicates these three AFAP family members participate in tumor progression, but their clinical significance and molecular mechanisms in gastric cancer (GC) remain unclear. Methods We first analyzed expression of AFAP family genes using public datasets and verified the results. The clinical significance of AFAP family genes in GC patients was also analyzed. In vitro and in vivo experiments were applied to explore the function of AFAP1L1. Enrichment analysis was used to explore potential molecular mechanisms. We then performed additional experiments, such as cell adhesion assay, co-immunoprecipitation and so on to confirm the downstream molecular mechanisms of AFAP1L1. Results Public data analyses and our verification both showed AFAP1L1 was the only AFAP family members that was significantly upregulated in GC compared with normal gastric tissues. Besides, only AFAP1L1 could predict poor prognosis and act as an independent risk factor for GC patients. In addition, AFAP1L1 promotes GC cells proliferation, migration, invasion in vitro and tumor growth, metastasis in vivo by inducing epithelial-to-mesenchymal transition (EMT). In terms of mechanism, AFAP1L1 interacts with VAV guanine nucleotide exchange factor 2 (VAV2) to activate Rho family GTPases CDC42, which finally promotes expression of integrin subunit alpha 5 (ITGA5) and activation of integrin signaling pathway. Conclusion AFAP1L1 promotes GC progression by inducing EMT through VAV2-mediated activation of CDC42 and ITGA5 signaling pathway, indicating AFAP1L1 may be a promising prognostic biomarker and therapeutic target for GC patients.
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页数:18
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