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- Title
Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue.
- Authors
Zakic, Tamara; Kalezic, Andjelika; Drvendzija, Zorka; Udicki, Mirjana; Ivkovic Kapicl, Tatjana; Srdic Galic, Biljana; Korac, Aleksandra; Jankovic, Aleksandra; Korac, Bato
- Abstract
The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.
- Subjects
ADIPOSE tissues; BREAST; OBESITY in women; BREAST cancer; METABOLIC reprogramming; CITRATE synthase; LIPOLYSIS
- Publication
Cells (2073-4409), 2024, Vol 13, Issue 2, p155
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells13020155