Scholarlink

<p>Ferroptosis, an iron-dependent form of programmed cell death driven by toxic lipid peroxide accumulation, plays a critical role in various diseases, making its modulation a promising therapeutic strategy. In this study, we identified defactinib, a specific inhibitor of FAK as a novel ferroptosis suppressors. We demonstrate that FAK/SRC-JNK signaling positively regulates ferroptosis by upregulating ACSL4, a critical mediator of ferroptosis. We reveal that a subset of JNK downstream transcription factors, including ATF2, NFATC1, NFATC3, and SMAD4, promote ferroptosis through direct binding to the ACSL4 promoter and activation of its expression. In contrast, another subset of JNK-associated transcription factors, including c-Jun, STAT3, ELK1, and HSF1, inhibit ferroptosis by binding to the ACSL4 promoter and repressing its expression. The net effect of FAK/SRC-JNK signaling in our models is a significant upregulation of ACSL4 and promotion of ferroptosis. Notably, elevated FAK/SRC-JNK signaling sensitizes cancer cells to ferroptosis-inducing therapies, while inhibition of the FAK/SRC-JNK signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings highlight the central role of FAK/ SRC-JNK signaling in controlling ferroptotic cell death and underscore the therapeutic potential of targeting FAK/ SRC-JNK mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.</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

FAK/SRC-JNK axis promotes ferroptosis via upregulating ACSL4 expression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月20日

查看全文
  • Jianhua Qin,
  • Shuang Ma,
  • Junyang Wang,
  • Siyuan Huang,
  • Jing Luan,
  • Jiyuan He,
  • Guoyuan Hou,
  • Na Sun,
  • Wei Zhang,
  • Minghui Gao

摘要

Ferroptosis, an iron-dependent form of programmed cell death driven by toxic lipid peroxide accumulation, plays a critical role in various diseases, making its modulation a promising therapeutic strategy. In this study, we identified defactinib, a specific inhibitor of FAK as a novel ferroptosis suppressors. We demonstrate that FAK/SRC-JNK signaling positively regulates ferroptosis by upregulating ACSL4, a critical mediator of ferroptosis. We reveal that a subset of JNK downstream transcription factors, including ATF2, NFATC1, NFATC3, and SMAD4, promote ferroptosis through direct binding to the ACSL4 promoter and activation of its expression. In contrast, another subset of JNK-associated transcription factors, including c-Jun, STAT3, ELK1, and HSF1, inhibit ferroptosis by binding to the ACSL4 promoter and repressing its expression. The net effect of FAK/SRC-JNK signaling in our models is a significant upregulation of ACSL4 and promotion of ferroptosis. Notably, elevated FAK/SRC-JNK signaling sensitizes cancer cells to ferroptosis-inducing therapies, while inhibition of the FAK/SRC-JNK signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings highlight the central role of FAK/ SRC-JNK signaling in controlling ferroptotic cell death and underscore the therapeutic potential of targeting FAK/ SRC-JNK mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.