PhD Scientific Days 2026

Pathological and Oncological Sciences 1.

Fatty acid synthesis is critical for sustaining TORC1 activity in malignant tumors

Name of the presenter

Károlyi, Dorottya

Institute/workplace of the presenter

Eötvös Loránd University

Authors

Dorottya Károlyi¹, Bálint Sólyom Bótor², Natali Neuhauser¹, Mária Péter³, Gábor Balogh³, Fergal O'Farrell⁴, Szabolcs Takáts¹
1: Faculty of Science, Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Hungary
2: Faculty of Science, Department of Biochemistry, Eötvös Loránd University, Hungary
3: Molecular Stress Biology Group, Institute of Biochemistry, HUN-REN Biological Research Centre of Szeged
4: Faculty of Mathematics and Natural Sciences, Department of Biosciences, University of Bergen

Text of the abstract

Introduction
Lipid biosynthesis is essential for cellular homeostasis, yet its specific roles in malignant progression remain poorly understood. While metabolic reprogramming is a hallmark of cancer, the precise mechanisms by which de novo lipogenesis interacts with major growth-regulating pathways, such as TORC1, require deeper investigation in complex in vivo environments.
Aims
This study aims to identify critical metabolic vulnerabilities in malignant tumors using a Drosophila model. Specifically, we investigate the role of Acetyl-CoA carboxylase (ACC), a key enzyme in fatty acid synthesis, in regulating tumor growth, lipid composition, and TORC1 signaling.
Methods
We utilized a Drosophila Ras;Scribble tumor model for a targeted genetic screen. We employed RNA interference to silence ACC and monitored tumor progression and cell death. Changes in the lipidome were analyzed via lipidomics. To explore the signaling hierarchy, we performed genetic epistatic experiments by silencing PTEN, TSC1, or AMPK to attempt TORC1 reactivation. Finally, ex vivo oleic acid supplementation was conducted to validate the model's sensitivity to metabolic interventions.
Results
Silencing ACC significantly inhibited late-stage tumor growth and induced apoptosis. Lipidomic analysis confirmed a drastic reduction in newly synthesized neutral and membrane lipids. Notably, loss of ACC led to a marked reduction in TORC1 activity and induced autophagy. Genetic attempts to reactivate TORC1 via PTEN, TSC1, or AMPK silencing resulted in minimal recovery, suggesting that fatty acid synthesis regulates TORC1 through mechanisms distinct from classical insulin signaling. Ex vivo experiments showed that oleic acid treatment partially restores growth in ACC-deficient tumors.
Conclusion
Our findings highlight the critical role of de novo lipogenesis in sustaining TORC1 activity and driving tumor growth. The results suggest a non-canonical regulatory link between fatty acid synthesis and TORC1. This study establishes a rapid, cost-effective preclinical Drosophila system that bridges the gap between cell cultures and complex mammalian models for identifying novel metabolic therapeutic targets in oncology.
Funding
Supported by the MTA University Excellence Fund, the NKFIH, and the ÚNKP.
e-mail: dorottya.karolyi@gmail.com
Institute: Eötvös Loránd University
Supervisor: Dr. Szabolcs Takáts