南方医科大学学报2025，Vol.45Issue(5)：1031-1038,8.DOI:10.12122/j.issn.1673-4254.2025.05.16
过表达RGL1通过激活CDC42/RAC1复合体上调运动型黏着斑组装促进结直肠癌转移
RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assembly via activating the CDC42/RAC1 complex
摘要
Abstract
Objective To investigate the regulatory role of Ral guanine nucleotide dissociation stimulator-like 1(RGL1)in metastasis of colorectal cancer(CRC).Methods We analyzed the differential expression of RGL1 between metastatic and non-metastatic CRC in GEO database,and examined its expression in 25 patients with metastatic CRC and 25 patients with non-metastatic CRC treated in Zhujiang Hospital between January,2020 and December,2022 using quantitative PCR(qPCR)and immunohistochemistry.HCT116 cell lines with stable RGL1 overexpression and SW480 cells with RGL1 knockdown were established using lentiviral vecors,and the changes in invasion and migration abilities of the cells were assessed using Transwell invasion and migration assays.The transduced cells were injected into the serosa of the cecum of nude mice,and tumor growth and liver metastasis were observed 8 weeks later.Fibronectin adhesion assays and immunofluorescence experiments were employed to assess the relationship between RGL1 and focal adhesion formation,and co-immuno-precipitation assays were performed to explore the interaction between RGL1 and GTPase activation.Results Compared with non-metastatic CRC,metastatic CRC showed significantly upregulated expression of RGL1.HCT116 cells overexpressing RGL1 exhibited obviously enhanced migration and invasion in vitro with increased capacity for liver metastasis in nude mice.RGL1 overexpression strongly accelerated focal adhesion assembly,facilitated the formation of motile focal adhesions,and enhanced the binding of activated CDC42/RAC1 complex to RGL1.Conclusion RGL1 is highly expressed in metastatic CRC and promotes distant metastasis of CRC by activating the CDC42/RAC1 complex to facilitate the formation of motile focal adhesions.These findings suggest that RGL1 can potentially serve as a therapeutic target for CRC metastasis.关键词
RGL1/转移性结直肠癌/运动型黏着斑/CDC42/RAC1Key words
Ral guanine nucleotide dissociation stimulator-like 1/metastatic colorectal cancer/motile focal adhesion/CDC42/RAC1引用本文复制引用
翁诺舟,谭彬,曾文涛,古家宇,翁炼基,郑克鸿..过表达RGL1通过激活CDC42/RAC1复合体上调运动型黏着斑组装促进结直肠癌转移[J].南方医科大学学报,2025,45(5):1031-1038,8.基金项目
广东省自然科学基金(2020A1515010212) （2020A1515010212）
广州市基础研究计划项目(2024A04J9992) （2024A04J9992）
