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<p>Resistance to 5-fluorouracil (5-FU) remains a major challenge in the treatment of colorectal cancer (CRC). Here, we identify ETS variant transcription factor 7 (ETV7) as significantly upregulated in CRC tissues and cell lines, with elevated expression associated with poor clinical prognosis. Functional assays demonstrate that ETV7 enhances CRC cell proliferation, invasion, and resistance to 5-FU. Mechanistically, ETV7 transcriptionally upregulates CXCL1, leading to increased neutrophil recruitment and enhanced formation of neutrophil extracellular traps (NETs). The resulting NETs-enriched tumor microenvironment promotes tumor aggressiveness and chemoresistance. Pharmacological inhibition of CXCL1 or degradation of NETs effectively attenuates ETV7-driven malignant phenotypes in vitro and in vivo. Collectively, these findings establish an ETV7–CXCL1–NETs axis that contributes to 5-FU resistance in CRC and suggest that targeting this pathway may improve chemotherapy response.</p>

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ETV7 promotes 5-FU resistance and malignant progression through CXCL1-induced NETs formation in colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月31日

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  • Shuang Mo,
  • Pei Xia,
  • Yongrui Lv,
  • Lei Liu,
  • Shujin He,
  • Huabin Gao,
  • Lin Chen,
  • Jianqiang Wu,
  • Anjia Han,
  • Lixia Chen

摘要

Resistance to 5-fluorouracil (5-FU) remains a major challenge in the treatment of colorectal cancer (CRC). Here, we identify ETS variant transcription factor 7 (ETV7) as significantly upregulated in CRC tissues and cell lines, with elevated expression associated with poor clinical prognosis. Functional assays demonstrate that ETV7 enhances CRC cell proliferation, invasion, and resistance to 5-FU. Mechanistically, ETV7 transcriptionally upregulates CXCL1, leading to increased neutrophil recruitment and enhanced formation of neutrophil extracellular traps (NETs). The resulting NETs-enriched tumor microenvironment promotes tumor aggressiveness and chemoresistance. Pharmacological inhibition of CXCL1 or degradation of NETs effectively attenuates ETV7-driven malignant phenotypes in vitro and in vivo. Collectively, these findings establish an ETV7–CXCL1–NETs axis that contributes to 5-FU resistance in CRC and suggest that targeting this pathway may improve chemotherapy response.