Fatty acid-binding protein 2 suppresses liver metastasis by cytoplasmic sequestration of β-catenin to enhance ferroptosis sensitivity in colon cancer.
14 affiliations
- 1Department of Colorectal Cancer Center, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.
- 2The Guizhou Provincial Key Laboratory of Digestive System Diseases, Guiyang, Guizhou Province, China.
- 3Department of Infectious Diseases, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.
- 4School of Clinical Medicine, Guizhou Medical University, Guiyang, China.
- 5Key Laboratory of Hepatobiliary and Pancreatic Diseases Treatment and Bioinformatics Research, Guizhou Medical University, Guiyang, China.
- 6Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China.
- 7Department of Colorectal Cancer Center, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China. [email protected].
- 8The Guizhou Provincial Key Laboratory of Digestive System Diseases, Guiyang, Guizhou Province, China. [email protected].
- 9The Guizhou Provincial Key Laboratory of Digestive System Diseases, Guiyang, Guizhou Province, China. [email protected].
- 10Key Laboratory of Hepatobiliary and Pancreatic Diseases Treatment and Bioinformatics Research, Guizhou Medical University, Guiyang, China. [email protected].
- 11Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China. [email protected].
- 12The Guizhou Provincial Key Laboratory of Digestive System Diseases, Guiyang, Guizhou Province, China. [email protected].
- 13Key Laboratory of Hepatobiliary and Pancreatic Diseases Treatment and Bioinformatics Research, Guizhou Medical University, Guiyang, China. [email protected].
- 14Department of Hepatobiliary Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China. [email protected].
Abstract
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.
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BibTeX
@article{wu2026fatty,
title = {{Fatty acid-binding protein 2 suppresses liver metastasis by cytoplasmic sequestration of β-catenin to enhance ferroptosis sensitivity in colon cancer.}},
author = {Long Wu and Huan Wu and Yu-Tong Zhou and Guang-Ling Ou and Yong Sun and Xiao-Yun Li and Yun-Huan Zhen and Kun Cao and Hai-Yang Li},
journal = {Cell death \& disease},
year = {2026},
month = aug,
doi = {10.1038/s41419-026-09161-7},
url = {https://europepmc.org/article/MED/42957643},
note = {CC BY},
}
RIS
TY - JOUR
TI - Fatty acid-binding protein 2 suppresses liver metastasis by cytoplasmic sequestration of β-catenin to enhance ferroptosis sensitivity in colon cancer.
AU - Long Wu
AU - Huan Wu
AU - Yu-Tong Zhou
AU - Guang-Ling Ou
AU - Yong Sun
AU - Xiao-Yun Li
AU - Yun-Huan Zhen
AU - Kun Cao
AU - Hai-Yang Li
PY - 2026
DA - 2026/08/01
JO - Cell death & disease
DO - 10.1038/s41419-026-09161-7
UR - https://europepmc.org/article/MED/42957643
AB - 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.
SN - 2041-4889
ER -