The proteomics analysis of mitochondria-enriched fractions reveals alteration of key mitochondrial pathways in breast cancer cell lines
Por:
Vázquez-Narváez, HD, Labra-Barrios, ML, Ríos-Castro, E, Castañón-Sánchez, CA, Uribe-Carvajal, S, Hernández-Martínez, E, Hernández-Hernández, JM, León-Avila, G, Pérez-Rangel, A, Angeles-Morales, EB, Luna-Arias, JP
Publicada:
15 jun 2026
Resumen:
Breast cancer, the leading cause of death in women worldwide, shows significant heterogeneity that makes this disease extremely difficult to treat. Many reports point to metabolic shifts, mainly those carried out into mitochondria, as key processes governing the behavior and heterogeneity of several types of breast cancer. In this study, we performed label-free proteomics analysis on mitochondria-enriched fractions from T47D and MDA-MB231 breast cancer cell lines, which have distinct molecular classifications, using bioinformatics analyses to identify differentially expressed proteins compared to MCF-12F healthy breast cells. Cancer cells exhibited downregulated protein levels of subunits from the respiratory chain's Complex I. However, both showed differentially abundant proteins involved in ligase and oxidoreductase activities, including enzymes of glycolysis, pyruvate metabolism, the Krebs cycle, and gluconeogenesis. Many of these enzymes also participate in other metabolic processes, such as mitochondrial localization, mitochondrial gene expression, and the metabolism of amino acids, fatty acids, purines, and pyrimidines. Gene Set Enrichment Analysis revealed that OXPHOS subunits are integrated as signatures of neurodegenerative disease pathways. A protein set with little or no evidence in breast cancer was identified, which could lead to future research in breast cancer mitochondrial metabolism. Data are available via ProteomeXchange with identifier PXD069883. Significance: This manuscript determined the protein expression profiles of mitochondria-enriched fractions from T47D (Luminal A, stage IV) and MDA-MB-231 (triple negative, Stage IV) breast cancer cell lines compared to the MCF-12F healthy breast cell line. We found that breast cancer cell lines exhibited low expression levels of Complex I subunits from the respiratory chain. However, both breast cancer cell lines presented high expression levels of some proteins related to ligase and oxidoreductase activities, the latter on CH-OH groups in cellular respiration processes, such as some enzymes from glycolysis, pyruvate metabolism, Krebs cycle and gluconeogenesis. Moreover, many of these enzymes also participate in other metabolic processes, such as localization to the mitochondrion, mitochondrial gene expression, amino acid, fatty acid, purine, and pyrimidine metabolism. We also observed through Gene Set Enrichment Analysis that OXPHOS enzymes have a key role in many neurodegenerative disease pathways as well. Finally, we found a protein set with little or no evidence in breast cancer that could lead to future pivotal research in the mitochondrial metabolism of breast cancer.
Filiaciones:
Cinvestav, Natl Polytech Inst, Ctr Res & Adv Studies, Dept Cell Biol, Ave IPN 2508,Col San Pedro Zacatenco, Mexico City 07360, Mexico
Cinvestav, Unidad Genom Prote & Metabol, Natl Lab Expt Resources LaNSE, Ave IPN 2508,Col San Pedro Zacatenco,Alcaldia Gust, Mexico City 07360, Mexico
High Specialty Reg Hosp Oaxaca, Lab Biomed Res, Subdirecc Ensenanza Invest, C Aldama S-N,Paraje El Tule, San Bartolo Coyotepec 71294, Oaxaca, Mexico
Natl Autonomous Univ Mexico UNAM, Inst Cellular Physiol, Dept Mol Genet, Mexico City, Mexico
Escuela Nacl Ciencias Biol Inst Politecn Nacl ENCB, Unidad Profes Lazaro Cardenas, Dept Zool, Prolongac Carpio & Plan Ayala S-N,Col Santo Tomas, Mexico City 11340, Mexico
Escuela Nacl Ciencias Biol Inst Politecn Nacl ENCB, Unidad Profes Lazaro Cardenas, Dept Microbiol, Prolongac Carpio & Plan Ayala S-N,Col Santo Tomas, Mexico City 11340, Mexico
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