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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Primary Cilium Forces Neuroendocrine Shift in Prostate Cancer through YAP1 Repression and Reduced Mitochondrial
Yingbo Guo1,2, Siyong Peng1,2, Thibaud Jamet3,4
1Université Côte d'Azur, INSERM U1065, C3M, 151 Route de St Antoine de Ginestière, BP2 3194, CEDEX 03, 06204 Nice, France - Equipe 5.
Theranostics
|June 5, 2026
Summary
Primary cilia are linked to neuroendocrine prostate cancer progression and metabolic changes. Their presence in aggressive tumors suggests a role in disease adaptation and potential therapeutic targets.
Area of Science:
- Cell Biology
- Cancer Research
- Urology
Background:
- Primary cilia regulate cellular signaling and plasticity.
- Neuroendocrine (NE) prostate cancer is an aggressive subtype.
- Cilia are typically absent in localized prostate cancer but present in advanced disease.
Purpose of the Study:
- To investigate the distribution and role of primary cilia in NE prostate cancer.
- To explore the association between cilia, metabolic reprogramming, and NE features in CRPC.
- To identify potential biomarkers and therapeutic targets related to cilia in NEPC.
Main Methods:
- Detection of primary cilia in vitro and in vivo using prostate cancer models and patient samples.
- Analysis of tumor cell metabolism, including mitochondrial activity and FDG-PET positivity.
- Molecular profiling using GLI1, IFT20, IFT80, and YAP1 markers.
- Single-cell RNA sequencing to analyze gene expression in NE clusters.
Main Results:
- Primary cilia were detected in neuroendocrine-like cells in vitro and in CRPC samples.
- Cilia presence correlated with FDG-PET positivity and NE features in vivo.
- Aggressive tumors showed reduced mitochondrial activity, indicating a metabolic shift.
- A GLI1⁺/IFT20⁺ or GLI1⁺/IFT80⁺ signature was identified in ciliated, NE-prone subpopulations.
- Cytoskeletal remodeling induced partial NE transdifferentiation in vitro.
- Ciliogenesis-related genes were enriched in NE clusters in CRPC.
Conclusions:
- Primary cilia are associated with NE identity and metabolic adaptation in prostate cancer.
- Cilia play a functional role in NEPC progression, not just as passive markers.
- A structural-metabolic axis involving primary cilia may offer new biomarkers and therapeutic vulnerabilities.
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