FTO mediated glycolytic metabolism for papillary renal cell carcinoma immune evasion
N6-methyladenosine (m6A) methylation is the predominant internal modification in eukaryotic mRNA, characterized by the methylation of adenosine at the nitrogen-6 position. A key m6A demethylase, the Fat Mass and Obesity-associated protein (FTO) play a significant role in metabolism. Renal cell carcinoma (RCC), particularly papillary RCC, is characterized by increased glucose uptake and a shift towards anaerobic glycolysis, commonly known as the “Warburg effect”. This study investigates the role of FTO in glycolytic reprogramming and immune evasion in RCC. FTO disruption resulted in a Lactate Dehydrogenase A (LDHA) expression downregulation, followed by lactate production reduction and CD8 + T cells activation. Furthermore, FTO pharmacological inhibition by DAC51 promoted CD8 + T cell activation, also resulting in increased apoptotic activity. These findings reveal a novel role for FTO in regulating tumor metabolism and immune escape in pRCC, highlighting its potential as a therapeutic target for cancer immunotherapy.
Authors
- Manel Esteller (ORCID: https://orcid.org/0000-0003-4490-6093)
- Catarina Guimarães‐Teixeira (ORCID: https://orcid.org/0000-0003-2212-3872)
- Laura Martinez‐Verbo (ORCID: https://orcid.org/0000-0003-0817-3056)
- Cármen Jerónimo (ORCID: https://orcid.org/0000-0003-4186-5345)
- Vera Miranda‐Gonçalves (ORCID: https://orcid.org/0000-0002-4231-5532)
- Iola F. Duarte (ORCID: https://orcid.org/0000-0003-4289-9256)
- Alberto Bueno-Costa (ORCID: https://orcid.org/0000-0001-8700-2540)
- Rui Henrique (ORCID: https://orcid.org/0000-0003-3171-4666)
- Daniela Barros‐Silva (ORCID: https://orcid.org/0000-0001-6746-6807)
- João Lobo (ORCID: https://orcid.org/0000-0001-6829-1391)
- Sandra P. Nunes (ORCID: https://orcid.org/0000-0003-4466-037X)
- Íris R. Carriço
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universidade do Porto (PT)
- Research Institute Hospital 12 de Octubre (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Hospital Universitario 12 De Octubre (ES)
- IPO Porto (PT)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (ES)
- LAQV Requimte (PT)
- RISE - Health Research Network (PT)
- Instituto de Ciências Biomédicas Albel Salazar (PT)
- University of Aveiro (PT)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2026-10-31
- DOI
- https://doi.org/10.1016/j.biopha.2026.120009
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00