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Oleic acid-PPARγ-FABP4 loop fuels cholangiocarcinoma colonization in lymph node metastases microenvironment

  • 0Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Hepatology Forum +

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February 20, 2024

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February 20, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Cholangiocarcinoma cells reprogram lipid metabolism to colonize lymph nodes, driven by an oleic acid-PPARγ-FABP4 loop. Targeting this loop offers a promising strategy to inhibit metastasis and improve patient outcomes.

Area Of Science

  • Oncology
  • Metabolic Biology
  • Cancer Metastasis

Background

  • Lymph node metastasis is a critical factor in cholangiocarcinoma patient prognosis.
  • The mechanisms of cholangiocarcinoma adaptation within the lymph node microenvironment are not well understood.

Purpose Of The Study

  • To investigate if metabolic reprogramming drives cholangiocarcinoma cell adaptation and remodeling in lymph nodes.
  • To identify key metabolic pathways and regulators involved in lymph node metastasis.

Main Methods

  • Single-cell RNA sequencing of primary tumors and lymph node metastases.
  • Pan-cancer single-cell RNA sequencing analysis.
  • Metabolomics and in vivo CRISPR/Cas9 screening.
  • Patient-derived organoids and animal models.

Main Results

  • Cholangiocarcinoma exhibits reduced intertumor heterogeneity and distinct lipid metabolic reprogramming in lymph node metastases.
  • The oleic acid-PPARγ-fatty acid-binding protein 4 (FABP4) feedback loop was identified as crucial for lymph node colonization by upregulating fatty acid uptake and oxidation.
  • Inhibition of this loop significantly impaired cholangiocarcinoma proliferation and colonization.
  • PPARγ-regulated lipid metabolism contributes to an immune-suppressive niche and is linked to tumor relapse and poor response to immunotherapy.

Conclusions

  • The oleic acid-PPARγ-FABP4 loop is essential for cholangiocarcinoma lymph node colonization.
  • Targeting PPARγ-regulated lipid metabolic reprogramming presents a promising therapeutic strategy for cholangiocarcinoma lymph node metastasis.
  • This approach may help reduce metastasis burden and disease progression.