Spatial Architecture of GLUT1 and Glycolytic Complexes in Breast Cancer
6 affiliations
- 1Department of Life Sciences, University of Trieste, 34127 Trieste, Italy
- 2Department of Medicine, Università degli Studi di Udine, 33100 Udine, Italy
- 3Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
- 4Center for Genetic Engineering (CEINGE)-Biotecnologie Avanzate Franco Salvatore, 80145 Naples, Italy
- 5Clinical Proteomics and Metabolomics Unit, School of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro, 20900 Monza, Italy
- 6Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Catholic University of the Sacred Heart, 00168 Rome, Italy
Abstract
Breast cancer cells exhibit a tight dependence on glucose metabolism, sustained both by the transcriptional deregulation of metabolism-related genes and the spatiotemporal organization of the glycolytic machinery across cellular compartments. Although the overexpression of GLUT1 and key glycolytic enzymes is a well-established hallmark of aggressive breast cancer subtypes, expression-level analyses sometimes fail to predict the increased glycolytic flux in breast cancer cells. Subcellular localisation is in fact a critical, yet underappreciated, regulatory layer controlling glycolytic flux. Key mechanisms contributing to this include the recruitment of glycolytic enzymes into dynamic cytoplasmic assemblies, the association of glycolytic enzymes and GLUT1 with membrane scaffolding platforms that concentrate glycolytic activity at sites of glucose entry and utilization, and their co-recruitment to endocytic vesicles enabling compartment-specific metabolic support. Specific protein–protein interactions determine these scenarios. We review both the conventional and emerging techniques to resolve the organizational complexity, as well as the functional and clinical implications, of this spatial regulatory layer in breast cancer. We highlight the spatial organization of GLUT1 and glycolytic enzymes as a critical determinant of glycolytic flux and suggest that disrupting their architecture may lead to new therapeutic strategies in breast cancer.
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BibTeX
@article{secco2026spatial,
title = {{Spatial Architecture of GLUT1 and Glycolytic Complexes in Breast Cancer}},
author = {Luca Secco and Martina Mascaro and Michele Costanzo and Lucia Santorelli and Riccardo Sgarra and Sara Petrosino},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191726},
url = {https://www.mdpi.com/2073-4409/15/19/1726},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial Architecture of GLUT1 and Glycolytic Complexes in Breast Cancer
AU - Luca Secco
AU - Martina Mascaro
AU - Michele Costanzo
AU - Lucia Santorelli
AU - Riccardo Sgarra
AU - Sara Petrosino
PY - 2026
DA - 2026/09/22
JO - Cells
DO - 10.3390/cells15191726
UR - https://www.mdpi.com/2073-4409/15/19/1726
AB - Breast cancer cells exhibit a tight dependence on glucose metabolism, sustained both by the transcriptional deregulation of metabolism-related genes and the spatiotemporal organization of the glycolytic machinery across cellular compartments. Although the overexpression of GLUT1 and key glycolytic enzymes is a well-established hallmark of aggressive breast cancer subtypes, expression-level analyses sometimes fail to predict the increased glycolytic flux in breast cancer cells. Subcellular localisation is in fact a critical, yet underappreciated, regulatory layer controlling glycolytic flux. Key mechanisms contributing to this include the recruitment of glycolytic enzymes into dynamic cytoplasmic assemblies, the association of glycolytic enzymes and GLUT1 with membrane scaffolding platforms that concentrate glycolytic activity at sites of glucose entry and utilization, and their co-recruitment to endocytic vesicles enabling compartment-specific metabolic support. Specific protein–protein interactions determine these scenarios. We review both the conventional and emerging techniques to resolve the organizational complexity, as well as the functional and clinical implications, of this spatial regulatory layer in breast cancer. We highlight the spatial organization of GLUT1 and glycolytic enzymes as a critical determinant of glycolytic flux and suggest that disrupting their architecture may lead to new therapeutic strategies in breast cancer.
SN - 2073-4409
ER -