南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (7): 1533-1542.doi: 10.12122/j.issn.1673-4254.2026.07.07

• • 上一篇    

CFL1及p-CFL在结肠癌中高表达预示结肠癌患者预后不良并促进癌细胞迁移

王琳钰1,2(), 王晓燕1,2,4, 朱季军1,2, 蒋波1,2, 徐洁1,2,4, 高彩月2,3,4, 李冬冬2,3,4, 王玉2,3,4, 李晓敏1,2,4()   

  1. 1.江苏省人民医院宿迁医院,消化内科,江苏 宿迁 223800
    2.江苏省人民医院宿迁医院,宿迁市结直肠癌及炎症性肠病基础与临床转化重点实验室,江苏 宿迁 223800
    3.江苏省人民医院宿迁医院,临床医学研究中心,江苏 宿迁 223800
    4.江苏省人民医院宿迁医院,神经与肿瘤药物研发全国重点实验室,江苏 宿迁 223800
  • 收稿日期:2026-01-26 出版日期:2026-07-20 发布日期:2026-07-20
  • 通讯作者: 李晓敏 E-mail:1007080916@qq.com;lxm1980326@sina.com
  • 作者简介:王琳钰,在读硕士研究生,E-mail: 1007080916@qq.com
  • 基金资助:
    国家自然科学基金(82573244);国家自然科学基金(81902479);江苏省卫健委医学科研项目(M2024038);广东省基础与应用基础研究基金(2021A1515010665);宿迁市科技计划(M202503);宿迁市科技计划(KY202304);宿迁英才雄英计划(SQXY202436);神经与肿瘤药物研发全国重点实验室开放课题(SKLSIM-20250701)

High expression of CFL1 and phospho-CFL1 predicts poor prognosis and promotes migration of colon cancer cells in vitro

Linyu WANG1,2(), Xiaoyan WANG1,2,4, Jijun ZHU1,2, Bo JIANG1,2, Jie XU1,2,4, Caiyue GAO2,3,4, Dongdong LI2,3,4, Yu WANG2,3,4, Xiaomin LI1,2,4()   

  1. 1.Department of Gastroenterology, Suqian Hospital of Jiangsu Provincial People's Hospital, Suqian 223800, China
    2.Suqian Key Laboratory of Basic and Clinical Translation for Colorectal Cancer and Inflammatory Bowel Disease, Suqian Hospital of Jiangsu Provincial People's Hospital, Suqian 223800, China
    3.Clinical Medical Research Center, Suqian Hospital of Jiangsu Provincial People's Hospital, Suqian 223800, China
    4.State Key Laboratory of Neurology and Oncology Drug Development, Suqian Hospital of Jiangsu Provincial People's Hospital, Suqian 223800, China
  • Received:2026-01-26 Online:2026-07-20 Published:2026-07-20
  • Contact: Xiaomin LI E-mail:1007080916@qq.com;lxm1980326@sina.com
  • Supported by:
    National Natural Science Foundation of China(82573244)

摘要:

目的 探究丝切蛋白1(CFL1)及其磷酸化形式p-CFL1在结肠癌中的表达情况,分析其与临床病理特征及预后的关系。揭示CFL1/p-CFL1调控结肠癌细胞迁移的分子机制,重点阐明其核定位在此过程中所发挥的作用及潜在机制。 方法 利用TCGA数据库、结肠癌组织芯片免疫组化分析CFL1和p-CFL1表达及临床病理参数相关性;应用Kaplan-Meier生存分析探究CFL1和p-CFL1表达水平与结肠癌患者生存期的关系;应用免疫荧光明确CFL1和p-CFL1在细胞核和细胞质的定位;构建野生型(CFL1-WT)与核定位信号突变型(CFL1-MUT)载体,在HCT116细胞中过表达,通过Transwell小室迁移实验检测细胞迁移能力;结合转录组测序与KEGG富集分析解析差异基因与信号通路。 结果 免疫组化结果显示,CFL1与p-CFL1在结肠癌组织中表达显著高于癌旁组织(P<0.0001),且二者表达呈正相关(r=0.4753,P<0.0001)。CFL1和p-CFL1高表达与淋巴结转移、临床分期晚及患者总生存期缩短相关(P<0.05)。免疫组化与免疫荧光显示CFL1/p-CFL1可定位于细胞质与细胞核。功能实验表明,过表达CFL1-WT与CFL1-MUT均能促进HCT116细胞迁移,且CFL1-WT作用更强。KEGG分析提示,CFL1-WT调控的基因显著富集于Ras、PI3K-Akt、细胞粘附分子等肿瘤转移相关通路。 结论 CFL1/p-CFL1在结肠癌中高表达,是预后不良的潜在生物标志物。CFL1可通过核定位进一步激活肿瘤转移相关信号通路,从而促进结肠癌迁移。

关键词: 结肠癌, 丝切蛋白1, 磷酸化形式丝切蛋白1, 核定位, 预后

Abstract:

Objective To investigate the expressions of cofilin-1 (CFL1) and its phosphorylated form p-CFL1 in colon cancer, their relationship with clinicopathological features and patient prognosis, and their regulatory roles in colon cancer cell migration. Methods The expression of CFL1 and p-CFL1 and their correlation with clinicopathological parameters were analyzed using the TCGA database and immunohistochemistry of colon cancer tissue microarrays. Kaplan-Meier survival analysis was used to explore the association of CFL1/p-CFL1 expression levels with survival of colon cancer patients. The localization of CFL1 and p-CFL1 in the nucleus and cytoplasm was observed using immunofluorescence staining. Wild-type (CFL1-WT) and nuclear localization signal mutant-type (CFL1-MUT) overexpression vectors were constructed and transfected into HCT116 cells, and the changes in cell migration were assessed using Transwell chamber migration assay. Transcriptome sequencing combined with KEGG enrichment analysis was performed to identify the differentially expressed genes and signaling pathways. Results Immunohistochemistry results showed significantly increased expressions of CFL1 and p-CFL1 in colon cancer tissues compared with the adjacent tissues (P<0.0001), and their expression levels were positively correlated (r=0.4753, P<0.0001). High expressions of CFL1 and p-CFL1 were significantly correlated with lymph node metastasis, advanced clinical stage, and shorter overall survival of the patients (P<0.05). Immunohistochemistry and immunofluorescence staining demonstrated localization of CFL1 and p-CFL1 in both the cytoplasm and nucleus. Functional experiments showed that overexpression of CFL1-WT and CFL1-MUT both promoted HCT116 cell migration, and CFL1-WT exhibited a stronger effect. KEGG analysis suggested that the genes regulated by CFL1-WT were significantly enriched in tumor metastasis-related pathways involving Ras, PI3K-Akt, and cell adhesion molecules. Conclusion CFL1/p-CFL1 are highly expressed in colon cancer and can be potential biomarkers for poor prognosis. CFL1 overexpression further activates tumor metastasis-related signaling pathways through nuclear localization, thereby promoting colon cancer migration.

Key words: colon cancer, cofilin-1, phosphorylated cofilin-1, nuclear localization, prognosis