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Updated: Aug 5, 2026
12:13
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer
Yang Zheng1, Caleb Cheng1, Yizhi Cao1
1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Biorxiv : the Preprint Server for Biology
|July 30, 2026
Summary
Neuroendocrine prostate cancer (NEPC) cells adapt to low oxygen by using PIKfyve to recycle lipids. Inhibiting PIKfyve and fatty acid synthase (FASN) together kills NEPC cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Neuroendocrine prostate cancer (NEPC) thrives in hypoxic conditions, but its metabolic adaptations are unclear.
- Understanding NEPC's response to metabolic stress is crucial for developing new therapies.
Purpose of the Study:
- To identify mechanisms of adaptation to hypoxic stress in NEPC.
- To investigate the role of the lipid kinase PIKfyve in NEPC survival.
- To explore therapeutic vulnerabilities in NEPC.
Main Methods:
- Analysis of PIKfyve expression in NEPC.
- Investigating PIKfyve's role in lysosomal function and lipid recycling under hypoxia.
- Assessing the impact of PIKfyve inhibition on endoplasmic reticulum (ER) stress and de novo lipogenesis.
- Evaluating the synergistic effect of dual PIKfyve and fatty acid synthase (FASN) inhibition.
Main Results:
- PIKfyve is overexpressed in NEPC and crucial for lysosomal degradation and lipid recycling under hypoxia.
- PIKfyve inhibition causes ER stress accumulation and activates compensatory lipogenesis.
- Dual inhibition of PIKfyve and FASN synergistically increases ER stress and induces NEPC cell death.
Conclusions:
- A stress-lipid kinase axis involving PIKfyve is essential for NEPC adaptation to hypoxia.
- Targeting PIKfyve and FASN simultaneously presents a promising therapeutic strategy for NEPC.
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