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<p>Resistance to platinum-based drugs represents a significant challenge in the clinical treatment of esophageal cancer. Particularly, some esophageal cancer patients exhibit primary resistance to platinum-based drugs. Our study revealed that the level of N-acetyltransferase 10 (NAT10) is inversely correlated with the efficacy of platinum-based drug neoadjuvant therapy. In the presence of oxaliplatin, NAT10 significantly reduced the cytotoxicity of oxaliplatin and enhanced esophageal cancer cells’ invasive, migratory, and clonogenic abilities. Mechanistically, oxaliplatin promoted the binding of NAT10 to PARP1. NAT10 acetylated PARP1 at the K97 site, thereby enhancing its stability. Additionally, acetylated PARP1 increased its PARylation modification, promoting the recruitment of downstream DNA repair proteins. In conclusion, NAT10 contributes to primary resistance by regulating the crosstalk of acetylation and PARylation of PARP1 in esophageal cancer.</p>

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NAT10-mediated crosstalk between acetylation and PARylation enhances the function of PARP1 promoting primary resistance in esophageal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月13日

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  • Yake Chen,
  • Sizhen Hou,
  • Boyuan Jiang,
  • Yang Yang,
  • Yisi Fan,
  • Xinyue Huang,
  • Fengxiang Liu,
  • Wenjing An,
  • Qiaocen Geng,
  • Jie Yin,
  • Huiqin Zheng,
  • Kexin Guo,
  • Ting Li,
  • Wenwen Zhao,
  • Zhijian Deng,
  • Di Han,
  • Heng Li,
  • Yu Song

摘要

Resistance to platinum-based drugs represents a significant challenge in the clinical treatment of esophageal cancer. Particularly, some esophageal cancer patients exhibit primary resistance to platinum-based drugs. Our study revealed that the level of N-acetyltransferase 10 (NAT10) is inversely correlated with the efficacy of platinum-based drug neoadjuvant therapy. In the presence of oxaliplatin, NAT10 significantly reduced the cytotoxicity of oxaliplatin and enhanced esophageal cancer cells’ invasive, migratory, and clonogenic abilities. Mechanistically, oxaliplatin promoted the binding of NAT10 to PARP1. NAT10 acetylated PARP1 at the K97 site, thereby enhancing its stability. Additionally, acetylated PARP1 increased its PARylation modification, promoting the recruitment of downstream DNA repair proteins. In conclusion, NAT10 contributes to primary resistance by regulating the crosstalk of acetylation and PARylation of PARP1 in esophageal cancer.