Related Experiment Video

Updated: Aug 5, 2026

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
10:38

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture

Published on: November 22, 2019

The FGFRL1-FASN axis regulates neuroendocrine lineage transdifferentiation by modulating fatty acid synthesis in AR

Yupeng Chen1, Jiarun Lai2, Jian Chen1

  • 1Department of Urology, School of Medicine, The Second Affiliated Hospital of South China University of Technology (Guangzhou First People's Hospital), Guangzhou, 510180, China.

Cancer Letters
|July 28, 2026
PubMed

Insights

Neuroendocrine prostate cancer (NEPC) is a low fatty acid synthesis state linked to poor survival. The FGFRL1-FASN metabolic axis regulates NEPC transdifferentiation and metastasis in AR pathway-independent prostate cancer.

Area of Science:

  • Oncology
  • Metabolic pathways
  • Cancer biology

Background:

  • AR pathway-independent prostate cancer (ARIPC), especially neuroendocrine prostate cancer (NEPC), is a lethal form of metastatic castration-resistant prostate cancer (mCRPC).
  • The role of fatty acid synthesis (FAS) in ARIPC and its influence on neuroendocrine lineage transdifferentiation are not well understood.

Purpose of the Study:

  • To investigate the organization of FAS in ARIPC.
  • To determine if distinct lipogenic states influence neuroendocrine lineage transdifferentiation.
  • To identify key molecular players in this process.

Main Methods:

  • Integration of single-cell and bulk transcriptomic analyses of mCRPC cohorts.
  • Functional studies involving depletion and restoration of fatty acid synthase (FASN) and FGFRL1.
  • Targeted gas chromatography-mass spectrometry (GC-MS) and fluorescent uptake assays.
  • Directional perturbation, rescue, AKT phosphorylation, and co-immunoprecipitation analyses.

Main Results:

  • NEPC is characterized as a fatty-acid-synthesis-low state associated with poor survival.
  • FASN is a key indicator and functional driver of lipogenic activity; its depletion suppresses lipogenesis but enhances NEPC programs and metastasis.
  • FGFRL1 is identified as a key regulator of FAS in ARIPC, influencing FASN expression and fatty acid content.
  • The FGFRL1-FASN axis was functionally validated, and ONECUT2 was identified as a downstream regulator.

Conclusions:

  • An FGFRL1-FASN metabolic axis plays a crucial role in regulating neuroendocrine lineage transdifferentiation.
  • This axis is implicated in the metastatic progression of AR pathway-independent prostate cancer.
  • Targeting this metabolic pathway may offer therapeutic strategies for aggressive prostate cancer.
Keywords:
AR pathway-independent prostate cancerFASNFGFRL1Fatty acid synthesisNeuroendocrine lineage transdifferentiation

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