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<p>Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B’s clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving &gt; 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.</p>

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Targeting KIF18B overcomes oxaliplatin resistance in esophageal squamous cell carcinoma via suppression of the ATR/CHK1 axis

  • 期刊论文

  • 发表日期：

    2026年5月27日

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  • Wei Liu,
  • Qianru Wang,
  • Xiao Tan,
  • Chunyu Cao,
  • Bole Tian

摘要

Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B’s clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving > 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.