Scholarlink

<p>Metastatic colon cancer commonly exhibits resistance to ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation. However, the mechanisms linking metabolic regulation to ferroptosis during metastatic progression remain incompletely understood. Here, we identified fatty acid-binding protein 2 (FABP2) as a regulator associated with ferroptosis sensitivity and liver metastatic phenotypes in colon cancer. Multi-omics analyses of clinical specimens showed reduced FABP2 expression in advanced colon cancer, which was associated with metastatic progression and poor survival. Mechanistically, FABP2 interacted with β-catenin, altered its intracellular localization, and was associated with reduced β-catenin/TCF4-dependent transcription of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis resistance. FABP2 overexpression increased ferroptosis sensitivity, whereas FABP2 downregulation promoted GPX4-dependent ferroptosis evasion and metastatic phenotypes. Pharmacological inhibition of Wnt/β-catenin signaling or GPX4 activity partially attenuated the effects of FABP2 loss. Together, these findings identify FABP2 as a factor associated with ferroptosis regulation and metastatic progression in colon cancer, and provide additional insight into the interplay between lipid metabolism, Wnt/β-catenin signaling, and ferroptosis.</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

Fatty acid-binding protein 2 suppresses liver metastasis by cytoplasmic sequestration of β-catenin to enhance ferroptosis sensitivity in colon cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月1日

查看全文
  • Long Wu,
  • Huan Wu,
  • Yu-Tong Zhou,
  • Guang-Ling Ou,
  • Yong Sun,
  • Xiao-Yun Li,
  • Yun-Huan Zhen,
  • Kun Cao,
  • Hai-Yang Li

摘要

Metastatic colon cancer commonly exhibits resistance to ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation. However, the mechanisms linking metabolic regulation to ferroptosis during metastatic progression remain incompletely understood. Here, we identified fatty acid-binding protein 2 (FABP2) as a regulator associated with ferroptosis sensitivity and liver metastatic phenotypes in colon cancer. Multi-omics analyses of clinical specimens showed reduced FABP2 expression in advanced colon cancer, which was associated with metastatic progression and poor survival. Mechanistically, FABP2 interacted with β-catenin, altered its intracellular localization, and was associated with reduced β-catenin/TCF4-dependent transcription of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis resistance. FABP2 overexpression increased ferroptosis sensitivity, whereas FABP2 downregulation promoted GPX4-dependent ferroptosis evasion and metastatic phenotypes. Pharmacological inhibition of Wnt/β-catenin signaling or GPX4 activity partially attenuated the effects of FABP2 loss. Together, these findings identify FABP2 as a factor associated with ferroptosis regulation and metastatic progression in colon cancer, and provide additional insight into the interplay between lipid metabolism, Wnt/β-catenin signaling, and ferroptosis.