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Interleukin-17 receptor A drives cancer stem-like properties in colorectal cancer through STAT3 activation.

Jeng-Kai Jiang1,2,3, Chi-Hung Lin4,5,6, Chun-Chi Lin1,2

  • 1School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Journal of Cancer
|December 24, 2025
PubMed
Summary

Interleukin 17 receptor A (IL-17RA) promotes colorectal cancer (CRC) stem-like properties, worsening prognosis and chemoresistance. Targeting the IL-17RA-STAT3 axis offers a new therapeutic strategy for CRC patients.

Keywords:
STAT3cancer stem cellcolorectal cancerinterleukin-17 receptor Aself-renewal

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer stem cells (CSCs) drive tumor relapse, metastasis, and therapy resistance in colorectal cancer (CRC).
  • Interleukin 17 receptor A (IL-17RA) is implicated in CRC pathogenesis and progression, with reduced expression linked to better prognosis.

Purpose of the Study:

  • To investigate the role of IL-17RA in promoting CSC properties.
  • To assess the impact of IL-17RA on CRC prognosis and chemoresistance.

Main Methods:

  • Quantitative real-time polymerase chain reaction and Western blotting assessed IL-17RA and CSC marker expression.
  • Kaplan-Meier analysis evaluated the association between IL-17RA expression and clinical outcomes in 68 CRC patients.
  • Functional studies involved CRC cells with stable IL-17RA overexpression and treatment with IL-17RA signaling inhibitors.

Main Results:

  • High IL-17RA expression correlated with poor clinical outcomes in CRC patients.
  • IL-17RA overexpression increased CSC marker expression (CD133, LGR5, SOX2), enhanced sphere formation, and boosted 5-fluorouracil resistance.
  • STAT3 inhibition reduced CSC markers, sphere formation, and chemoresistance, revealing an IL-17RA-STAT3 axis.

Conclusions:

  • IL-17RA promotes CSC properties and chemoresistance in CRC via the STAT3 pathway.
  • IL-17RA serves as a potential prognostic biomarker and therapeutic target for colorectal cancer.