Scholarlink

Objective <p>This study investigated how granulocyte colony-stimulating factor (G-CSF) regulates colon cancer (CC) progression through epigenetic activation of the kruppel-like factor 5 (KLF5)/chemokine receptor type 4 (CXCR4) axis.</p> Methods <p>Human CC LoVo cells were exposed to G-CSF (20&#xa0;ng/mL) alone in combination with si-KLF5, oe-CXCR4, or the CXCR4 antagonist AMD3100 for 24&#xa0;h. Malignant behaviors were evaluated by CCK-8, colony formation, and Transwell assays. H3K27ac modification on the KLF5 promoter and KLF5 binding to the CXCR4 promoter were examined using immunofluorescence, dual-luciferase reporter, and ChIP assays. An orthotopic LoVo xenograft mouse model was used to assess tumor growth, metastasis, and epithelial–mesenchymal transition (EMT) marker expression. KLF5 and CXCR4 mRNA and protein levels were measured in CC cells and tissues via RT-qPCR and western blot.</p> Results <p>G-CSF&#xa0;enhanced LoVo cell proliferation, migration, and invasion in a dose-dependent manner, concomitant with increased H3 acetylation and histone H3 lysine 27 (H3K27ac) acetylation. Mechanistically, G-CSF upregulated KLF5 expression via H3K27ac modification, promoting CXCR4 transcriptional activation. Inhibition of KLF5 or CXCR4 partially reversed G-CSF-induced EMT and malignant phenotypes. In vivo, G-CSF accelerated tumor growth and metastasis through the KLF5/CXCR4 signaling pathway, confirming its pro-tumorigenic role.</p> Conclusions <p>G-CSF drives CC progression by enhancing H3K27ac-dependent upregulation of KLF5, which transactivates CXCR4 to promote EMT, proliferation and metastasis. Targeting the G-CSF/KLF5/CXCR4 axis may represent a potential therapeutic strategy for advanced CC.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

G-CSF promotes H3K27ac-modified KLF5 to activate CXCR4 expression and drive colon cancer growth and metastasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月6日

查看全文
  • Guoqing Ma,
  • Jing Jiang,
  • Tingting He,
  • Canhui Jin,
  • Wenhao Wu,
  • Wufeng Fan,
  • Tianbao Wang,
  • Ping Zhou

摘要

Objective

This study investigated how granulocyte colony-stimulating factor (G-CSF) regulates colon cancer (CC) progression through epigenetic activation of the kruppel-like factor 5 (KLF5)/chemokine receptor type 4 (CXCR4) axis.

Methods

Human CC LoVo cells were exposed to G-CSF (20 ng/mL) alone in combination with si-KLF5, oe-CXCR4, or the CXCR4 antagonist AMD3100 for 24 h. Malignant behaviors were evaluated by CCK-8, colony formation, and Transwell assays. H3K27ac modification on the KLF5 promoter and KLF5 binding to the CXCR4 promoter were examined using immunofluorescence, dual-luciferase reporter, and ChIP assays. An orthotopic LoVo xenograft mouse model was used to assess tumor growth, metastasis, and epithelial–mesenchymal transition (EMT) marker expression. KLF5 and CXCR4 mRNA and protein levels were measured in CC cells and tissues via RT-qPCR and western blot.

Results

G-CSF enhanced LoVo cell proliferation, migration, and invasion in a dose-dependent manner, concomitant with increased H3 acetylation and histone H3 lysine 27 (H3K27ac) acetylation. Mechanistically, G-CSF upregulated KLF5 expression via H3K27ac modification, promoting CXCR4 transcriptional activation. Inhibition of KLF5 or CXCR4 partially reversed G-CSF-induced EMT and malignant phenotypes. In vivo, G-CSF accelerated tumor growth and metastasis through the KLF5/CXCR4 signaling pathway, confirming its pro-tumorigenic role.

Conclusions

G-CSF drives CC progression by enhancing H3K27ac-dependent upregulation of KLF5, which transactivates CXCR4 to promote EMT, proliferation and metastasis. Targeting the G-CSF/KLF5/CXCR4 axis may represent a potential therapeutic strategy for advanced CC.

Graphical Abstract