FOXC1 mediates the proliferation and apoptosis of colon cancer cells through the Rap1 signaling pathway
10.12354/j.issn.1000-8179.2025.20250622
- VernacularTitle:FOXC1通过Rap1信号通路介导结肠癌细胞增殖与凋亡的机制研究
- Author:
Fu XIAOXIA
1
;
Li RUI
;
Duan RUIMIN
;
Hao LIYAO
;
Jin YING
Author Information
1. 山西医科大学附属忻州医院,忻州市人民医院病理科(山西省 忻州市 034000)
- Publication Type:Journal Article
- Keywords:
colon cancer;
FOXC1;
Rap1;
proliferation;
apoptosis
- From:
Chinese Journal of Clinical Oncology
2025;52(13):649-655
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the expression characteristics and clinical significance of FOXC1 in colon cancer,and decipher its mo-lecular mechanism in regulating tumor cell proliferation and apoptosis.Methods:The GEPIA database was employed to analyze the expres-sion of FOXC1 and its correlation with prognosis in colon cancer.Differential expression of FOXC1 was detected by qRT-PCR and Western blot in colon cancer cells(HCT116 and SW620)and normal colon epithelial cells(NCM460),and stable FOXC1-knockdown(sh-FOXC1)cell lines were established.Western blot,flow cytometry,CCK-8,and plate colony formation assays were performed to analyze the effects of FOXC1 knockdown on cell proliferation,cell cycle,and apoptosis.Furthermore,the downstream signaling pathway was verified using Rap1 overexpression rescue experiments.Results:FOXC1 mRNA expression was significantly higher in colon cancer tissues than in normal tissues(P<0.001).FOXC1 overexpression was nearing significance in relation to tumor staging(P=0.053),and patients with high FOXC1 expression had a shorter overall survival(Log-rank P=0.013).After FOXC1 knockdown,the expression of CyclinD1 and Bcl-2 decreased,whereas the ex-pression of Bax increased(P<0.01).The proportion of cells in the G0/G1 phase increased,while the proportion of cells in the S phase de-creased(P<0.001),and the cell proliferation activity and number of colonies formed decreased(P<0.001).Mechanistic studies demonstrated that after FOXC1 knockdown,Rap1 expression was reduced,while the expression of Rap1GAP increased(P<0.05).After restoration of Rap1 expression in FOXC1-knockdown cells,the downregulation of CyclinD1 and Bcl-2 expression and the increase in Bax expression were re-versed(P<0.05),the S phase ratio was increased(P<0.05),and cell proliferation activity and colony formation abilities were also re-scued.Conclusion:FOXC1 promotes colon cancer progression by facilitating Rap1 expression and downregulating Rap1GAP.Targeted inter-vention of the FOXC1-Rap1 signaling axis may emerge as a potential therapeutic strategy.
