Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026
[High expression of CFL1 and phospho-CFL1 predicts poor prognosis and promotes migration of colon cancer cells in vitro].
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Wang Linyu, Wang Xiaoyan, Zhu Jijun, Jiang Bo, Xu Jie, Gao Caiyue, Li Dongdong, Wang Yu, Li Xiaomin
Аннотация
OBJECTIVES: 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.