Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue
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 d...
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MDPI AG
2024-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/2/155 |
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| author | Tamara Zakic Andjelika Kalezic Zorka Drvendzija Mirjana Udicki Tatjana Ivkovic Kapicl Biljana Srdic Galic Aleksandra Korac Aleksandra Jankovic Bato Korac |
| author_facet | Tamara Zakic Andjelika Kalezic Zorka Drvendzija Mirjana Udicki Tatjana Ivkovic Kapicl Biljana Srdic Galic Aleksandra Korac Aleksandra Jankovic Bato Korac |
| author_sort | Tamara Zakic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T09:56:20Z |
| format | Article |
| id | doaj.art-e987ab8342a34f55a34e5e02e9a83118 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:56:20Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e987ab8342a34f55a34e5e02e9a831182024-01-29T13:50:25ZengMDPI AGCells2073-44092024-01-0113215510.3390/cells13020155Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose TissueTamara Zakic0Andjelika Kalezic1Zorka Drvendzija2Mirjana Udicki3Tatjana Ivkovic Kapicl4Biljana Srdic Galic5Aleksandra Korac6Aleksandra Jankovic7Bato Korac8Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaFaculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaFaculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaFaculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaFaculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaFaculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaThe 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.https://www.mdpi.com/2073-4409/13/2/155breast cancermitochondriametabolism |
| spellingShingle | Tamara Zakic Andjelika Kalezic Zorka Drvendzija Mirjana Udicki Tatjana Ivkovic Kapicl Biljana Srdic Galic Aleksandra Korac Aleksandra Jankovic Bato Korac Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue Cells breast cancer mitochondria metabolism |
| title | Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue |
| title_full | Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue |
| title_fullStr | Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue |
| title_full_unstemmed | Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue |
| title_short | Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue |
| title_sort | breast cancer mitochondria centered metabolic alterations in tumor and associated adipose tissue |
| topic | breast cancer mitochondria metabolism |
| url | https://www.mdpi.com/2073-4409/13/2/155 |
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