Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis
Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adi...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2731 |
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| author | Andjelika Kalezic Mirjana Udicki Biljana Srdic Galic Marija Aleksic Aleksandra Korac Aleksandra Jankovic Bato Korac |
| author_facet | Andjelika Kalezic Mirjana Udicki Biljana Srdic Galic Marija Aleksic Aleksandra Korac Aleksandra Jankovic Bato Korac |
| author_sort | Andjelika Kalezic |
| collection | DOAJ |
| description | Typical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue. |
| first_indexed | 2024-03-10T10:49:28Z |
| format | Article |
| id | doaj.art-187475a094064d43bb872effccb2dc6f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:49:28Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-187475a094064d43bb872effccb2dc6f2023-11-21T22:19:17ZengMDPI AGCancers2072-66942021-05-011311273110.3390/cancers13112731Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and GlycolysisAndjelika Kalezic0Mirjana Udicki1Biljana Srdic Galic2Marija Aleksic3Aleksandra Korac4Aleksandra Jankovic5Bato Korac6Department of Physiology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaDepartment of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, SerbiaCenter for Electron Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaCenter for Electron Microscopy, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Physiology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Physiology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaTypical features of the breast malignant phenotype rely on metabolic reprogramming of cancer cells and their interaction with surrounding adipocytes. Obesity is strongly associated with breast cancer mortality, yet the effects of obesity on metabolic reprogramming of cancer and cancer-associated adipose tissue remain largely unknown. Paired biopsies of breast tumor tissue and adipose tissue from premenopausal women were divided according to pathohistological analyses and body mass index on normal-weight and overweight/obese with benign or malignant tumors. We investigated the protein expression of key regulatory enzymes of glycolysis, pentose phosphate pathway (PPP), and glycogen synthesis. Breast cancer tissue showed a simultaneous increase in 5′-AMP-activated protein kinase (AMPK) protein expression with typical features of the Warburg effect, including hexokinase 2 (HK 2) overexpression and its association with mitochondrial voltage-dependent anion-selective channel protein 1, associated with an overexpression of rate-limiting enzymes of glycolysis (phosphofructokinase 1—PFK-1) and pentose phosphate pathway (glucose-6-phosphate dehydrogenase—G6PDH). In parallel, cancer-associated adipose tissue showed increased AMPK protein expression with overexpression of HK 2 and G6PDH in line with increased PPP activity. Moreover, important obesity-associated differences in glucose metabolism were observed in breast cancer tissue showing prominent glycogen deposition and higher glycogen synthase kinase-3 protein expression in normal-weight women and higher PFK-1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein expression in overweight/obese women. In conclusion, metabolic reprogramming of glycolysis contributes to tissue-specific Warburg effect in breast cancer and cancer-associated adipose tissue.https://www.mdpi.com/2072-6694/13/11/2731breast cancercancer-associated adipose tissueAMPKglycolysishexokinaseglycogen |
| spellingShingle | Andjelika Kalezic Mirjana Udicki Biljana Srdic Galic Marija Aleksic Aleksandra Korac Aleksandra Jankovic Bato Korac Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis Cancers breast cancer cancer-associated adipose tissue AMPK glycolysis hexokinase glycogen |
| title | Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis |
| title_full | Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis |
| title_fullStr | Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis |
| title_full_unstemmed | Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis |
| title_short | Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis |
| title_sort | tissue specific warburg effect in breast cancer and cancer associated adipose tissue relationship between ampk and glycolysis |
| topic | breast cancer cancer-associated adipose tissue AMPK glycolysis hexokinase glycogen |
| url | https://www.mdpi.com/2072-6694/13/11/2731 |
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