TY  - JOUR
AU  - Zakić, Tamara
AU  - Kalezić, Anđelika
AU  - Drvendžija, Zorka
AU  - Udicki, Mirjana
AU  - Ivković Kapicl, Tatjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6528
AB  - 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.
PB  - Basel: MDPI
T2  - Cells
T1  - Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue
IS  - 2
VL  - 13
DO  - 10.3390/cells13020155
SP  - 155
ER  - 

@article{
author = "Zakić, Tamara and Kalezić, Anđelika and Drvendžija, Zorka and Udicki, Mirjana and Ivković Kapicl, Tatjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2024",
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.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue",
number = "2",
volume = "13",
doi = "10.3390/cells13020155",
pages = "155"
}

Zakić, T., Kalezić, A., Drvendžija, Z., Udicki, M., Ivković Kapicl, T., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2024). Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells
Basel: MDPI., 13(2), 155.
https://doi.org/10.3390/cells13020155

Zakić T, Kalezić A, Drvendžija Z, Udicki M, Ivković Kapicl T, Srdić Galić B, Korać A, Janković A, Korać B. Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells. 2024;13(2):155.
doi:10.3390/cells13020155 .

Zakić, Tamara, Kalezić, Anđelika, Drvendžija, Zorka, Udicki, Mirjana, Ivković Kapicl, Tatjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue" in Cells, 13, no. 2 (2024):155,
https://doi.org/10.3390/cells13020155 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5126
AB  - Altered redox homeostasis is recognized as a hallmark of neoplastic transformation. However, data from various in vitro and in vivo studies often show increased or decreased transcriptional and translational levels of antioxidant defense (AD) enzymes. One of the underlying causes for such conflicting reports is cell heterogeneity within the complex tumor microenvironment, especially in breast cancer. To overcome barriers associated with bulk tissue gene and protein expression analysis, we choose an immunohistochemical approach. We cross-examined serial tissue sections of tumor and adipose tissue from premenopausal women with malignant invasive ductal carcinoma and benign fibroadenoma to gain a comprehensive overview of cell-specific AD enzymes expression and localization patterns. At the level of overall tissue architecture, malignant tumor tissue shows significantly higher immunopositivity for copper, zinc- and manganese- superoxide dismutase, catalase, and glutathione peroxidase compared to benign tumor tissue. Generally, AD enzymes are specifically localized in the cytoplasm (copper, zinc superoxide dismutase, catalase, glutathione peroxidase) and mitochondria (manganese superoxide dismutase, glutathione peroxidase) of cancer cells and cancer-associated adipocytes. Detailed analysis of different regions of the tumor tissue revealed significant heterogeneity in the degree of immunopositivity along the axis of tumor center–invasive front–adipose tissue. Clusters of cancer cells at the invasive front of the tumor often show a higher degree of immunopositivity for AD enzymes compared to cancer cells in the center of the tumor mass. Similarly, cancer-associated adipocytes that are in close proximity to cancer cells at the invasive front of the tumor show a higher degree of immunopositivity for AD enzymes compared to adipocytes from distant peritumoral adipose tissue. In conclusion, immunohistochemical approach confirms high AD enzymes expression in breast cancer and further reveals distinct regional mosaicism consistent with cell heterogeneity within the tumor microenvironment. This research was supported by the Science Fund of the Republic of Serbia, #7750238-REFRAME.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue
DO  - 10.1016/j.freeradbiomed.2022.06.154
ER  - 

@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2022",
abstract = "Altered redox homeostasis is recognized as a hallmark of neoplastic transformation. However, data from various in vitro and in vivo studies often show increased or decreased transcriptional and translational levels of antioxidant defense (AD) enzymes. One of the underlying causes for such conflicting reports is cell heterogeneity within the complex tumor microenvironment, especially in breast cancer. To overcome barriers associated with bulk tissue gene and protein expression analysis, we choose an immunohistochemical approach. We cross-examined serial tissue sections of tumor and adipose tissue from premenopausal women with malignant invasive ductal carcinoma and benign fibroadenoma to gain a comprehensive overview of cell-specific AD enzymes expression and localization patterns. At the level of overall tissue architecture, malignant tumor tissue shows significantly higher immunopositivity for copper, zinc- and manganese- superoxide dismutase, catalase, and glutathione peroxidase compared to benign tumor tissue. Generally, AD enzymes are specifically localized in the cytoplasm (copper, zinc superoxide dismutase, catalase, glutathione peroxidase) and mitochondria (manganese superoxide dismutase, glutathione peroxidase) of cancer cells and cancer-associated adipocytes. Detailed analysis of different regions of the tumor tissue revealed significant heterogeneity in the degree of immunopositivity along the axis of tumor center–invasive front–adipose tissue. Clusters of cancer cells at the invasive front of the tumor often show a higher degree of immunopositivity for AD enzymes compared to cancer cells in the center of the tumor mass. Similarly, cancer-associated adipocytes that are in close proximity to cancer cells at the invasive front of the tumor show a higher degree of immunopositivity for AD enzymes compared to adipocytes from distant peritumoral adipose tissue. In conclusion, immunohistochemical approach confirms high AD enzymes expression in breast cancer and further reveals distinct regional mosaicism consistent with cell heterogeneity within the tumor microenvironment. This research was supported by the Science Fund of the Republic of Serbia, #7750238-REFRAME.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue",
doi = "10.1016/j.freeradbiomed.2022.06.154"
}

Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2022). Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe..
https://doi.org/10.1016/j.freeradbiomed.2022.06.154

Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;.
doi:10.1016/j.freeradbiomed.2022.06.154 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox mosaic in breast cancer: At the intersection of cancer and adipose tissue" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022),
https://doi.org/10.1016/j.freeradbiomed.2022.06.154 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33765617
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4175
AB  - One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.
PB  - Elsevier BV
T2  - Redox Biology
T1  - Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.
VL  - 41
DO  - 10.1016/j.redox.2021.101939
SP  - 101939
ER  - 

@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "One of the underlying mechanisms that could link breast cancer and obesity is shifted redox homeostasis in the tumor microenvironment. To reveal the relationship between the malignant phenotype and obesity, we compared redox profiles of breast tumor and tumor-associated adipose tissue from premenopausal women: normal-weight with benign tumors, overweight/obese with benign tumors, normal-weight with malignant tumors, and overweight/obese with malignant tumors. Namely, we examined the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression and activity of main antioxidant defense (AD) enzymes: copper, zinc- and manganese superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of 4-hydroxy-2-nonenal (4-HNE) modified proteins. Higher protein expression and activity of AD enzymes were found in malignant tumor tissue than benign tumor tissue, irrespective of obesity. Nevertheless, malignant tumor tissue of overweight/obese women was characterized by higher protein expression of Nrf2 and weaker immunopositivity for 4-HNE modified proteins. In malignant tumor-associated adipose tissue, the redox profile was clearly related to obesity. Higher Nrf2 protein expression and higher AD enzyme levels were observed in normal-weight women, while stronger immunopositivity for 4-HNE modified proteins was found in overweight/obese women. The results suggest that the complex interplay between obesity and malignancy involves redox-sensitive pathways in breast tumor and tumor-associated adipose tissue.",
publisher = "Elsevier BV",
journal = "Redox Biology",
title = "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.",
volume = "41",
doi = "10.1016/j.redox.2021.101939",
pages = "101939"
}

Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology
Elsevier BV., 41, 101939.
https://doi.org/10.1016/j.redox.2021.101939

Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy.. in Redox Biology. 2021;41:101939.
doi:10.1016/j.redox.2021.101939 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox profile of breast tumor and associated adipose tissue in premenopausal women - Interplay between obesity and malignancy." in Redox Biology, 41 (2021):101939,
https://doi.org/10.1016/j.redox.2021.101939 . .

TY  - JOUR
AU  - Korać, Aleksandra
AU  - Srdić-Galić, Biljana
AU  - Stančić, Ana
AU  - Otašević, Vesna
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2021
UR  - https://doi.org/10.5114/aoms/92118
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4197
AB  - Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.
PB  - Termedia Sp. z.o.o.
T2  - Archives of Medical Science
T1  - Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles
IS  - 2
VL  - 17
DO  - 10.5114/aoms/92118
SP  - 323
EP  - 336
ER  - 

@article{
author = "Korać, Aleksandra and Srdić-Galić, Biljana and Stančić, Ana and Otašević, Vesna and Korać, Bato and Janković, Aleksandra",
year = "2021",
abstract = "Introduction: Metabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lip-id storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT). Material and methods: Gene and protein expression levels of leptin, adi-ponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and "at risk" groups. Results: Compared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of "at risk" groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of "at risk" obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin. Conclusions: Low adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.",
publisher = "Termedia Sp. z.o.o.",
journal = "Archives of Medical Science",
title = "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles",
number = "2",
volume = "17",
doi = "10.5114/aoms/92118",
pages = "323-336"
}

Korać, A., Srdić-Galić, B., Stančić, A., Otašević, V., Korać, B.,& Janković, A.. (2021). Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science
Termedia Sp. z.o.o.., 17(2), 323-336.
https://doi.org/10.5114/aoms/92118

Korać A, Srdić-Galić B, Stančić A, Otašević V, Korać B, Janković A. Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles. in Archives of Medical Science. 2021;17(2):323-336.
doi:10.5114/aoms/92118 .

Korać, Aleksandra, Srdić-Galić, Biljana, Stančić, Ana, Otašević, Vesna, Korać, Bato, Janković, Aleksandra, "Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles" in Archives of Medical Science, 17, no. 2 (2021):323-336,
https://doi.org/10.5114/aoms/92118 . .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/11/2731
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4407
AB  - 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.
T2  - Cancers
T1  - Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis
IS  - 11
VL  - 13
DO  - 10.3390/cancers13112731
SP  - 2731
ER  - 

@article{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "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.",
journal = "Cancers",
title = "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis",
number = "11",
volume = "13",
doi = "10.3390/cancers13112731",
pages = "2731"
}

Kalezić, A., Udički, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2021). Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers, 13(11), 2731.
https://doi.org/10.3390/cancers13112731

Kalezić A, Udički M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis. in Cancers. 2021;13(11):2731.
doi:10.3390/cancers13112731 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Tissue-Specific Warburg Effect in Breast Cancer and Cancer-Associated Adipose Tissue—Relationship between AMPK and Glycolysis" in Cancers, 13, no. 11 (2021):2731,
https://doi.org/10.3390/cancers13112731 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udički, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4859
AB  - Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity
PB  - Elsevier BV
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer
VL  - 177
DO  - 10.1016/j.freeradbiomed.2021.08.086
SP  - S76
EP  - S77
ER  - 

@conference{
author = "Kalezić, Anđelika and Udički, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Breast cancer behaves as a complex pseudo-organ where the adaptive behavior of cancer cells is deeply context-dependent, reflecting various local and systemic influences. Recently, cancer-associated adipocytes emerged as critical players in cancer progression, adapting to metabolic demands of proliferating cancer cells and responding through the supply of diverse energy substrates. To decipher underlying mechanisms that enable such plastic response, we cross-examined biopsies of cancer-associated adipose tissue from normal-weight and overweight women with invasive ductal carcinoma compared to mammary adipose tissue of weight-matched women with benign fibroadenoma. To that end, we analyzed mitochondrial copy number and master regulators of energy and redox homeostasis (AMP-activated protein kinase – AMPK and nuclear factor erythroid 2-related factor 2 – Nrf2), followed by key enzymes in their downstream pathways such as glycolysis, pentose phosphate pathway, fatty acid oxidation, and antioxidant defense. Compared to mammary adipose tissue, cancer-associated adipose tissue showed concomitantly higher AMPK and Nrf2 protein expression followed by overexpression of hexokinase 2, glucose-6-phosphate dehydrogenase, peroxisomal acyl-coenzyme A oxidase 1, first-line antioxidant defense enzymes (CuZn- and Mn- superoxide dismutase and catalase), as well as higher mitochondrial copy number. In contrast, in cancer-associated adipose tissue of obese women, a sole increase in AMPK protein expression without Nrf2 was followed by increased protein expression of analyzed metabolic enzymes but not antioxidant defense enzymes or mitochondrial copy number. The results indicate that simultaneous activation of AMPK and Nrf2 signaling promotes a specific metabolic phenotype of cancer-associated adipose tissue, resembling the Warburg effect with high mitochondrial content and increased redox homeostasis threshold. Moreover, context-dependent disruption of the AMPK–Nrf2 axis could prevent the establishment of such phenotype in obesity",
publisher = "Elsevier BV, Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer",
volume = "177",
doi = "10.1016/j.freeradbiomed.2021.08.086",
pages = "S76-S77"
}

Kalezić, A., Udički, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2021). AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier BV., 177, S76-S77.
https://doi.org/10.1016/j.freeradbiomed.2021.08.086

Kalezić A, Udički M, Srdić Galić B, Korać A, Janković A, Korać B. AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;177:S76-S77.
doi:10.1016/j.freeradbiomed.2021.08.086 .

Kalezić, Anđelika, Udički, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "AMPK and Nrf2 drive redox-metabolic reprogramming of cancer-associated adipose tissue in breast cancer" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia, 177 (2021):S76-S77,
https://doi.org/10.1016/j.freeradbiomed.2021.08.086 . .

TY  - CONF
AU  - Kalezić, Anđelika
AU  - Udicki, Mirjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4681
AB  - Global trends of increasing caloric consumption and decreasing physical activity have given rise to metabolic diseases in epidemic proportions. As a chronic state of altered metabolic and energy homeostasis,obesity is associated with various chronic diseases, including cancer. Alongside obesity, breast cancer incidence is also on the rise,even among premenopausal women. Acting through systemic and local influences, obesity could be viewed as a potential driving force for breast cancer development; however, this relationship seems rather complex. Accumulating evidence indicates that obesity decreasesthe incidence of breast cancer but increases rates of mortality,metastasis and therapeutic resistance in premenopausal women. We aim to provide an in-depth insight into the molecular mechanisms underlying the intriguing relationship between breast cancer and obesity by focusing on cross-examinationof metabolic alterations in breast cancer and cancer-associated adipose tissue. Metabolic reprogramming will be discussed through the potential influences obesityexerts on major pathways in glucose, lipid, and mitochondrial metabolism in breast cancer and cancer-associated adipose tissue. An overview of the wide-ranging implications of context-dependent metabolic reprogramming for personalized diagnostic and therapeutic approaches will be given.
PB  - Belgrade: Serbian Nutrition Society
C3  - 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia
T1  - Molecular basis of obesity and cancer
SP  - 55
EP  - 55
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4681
ER  - 

@conference{
author = "Kalezić, Anđelika and Udicki, Mirjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Global trends of increasing caloric consumption and decreasing physical activity have given rise to metabolic diseases in epidemic proportions. As a chronic state of altered metabolic and energy homeostasis,obesity is associated with various chronic diseases, including cancer. Alongside obesity, breast cancer incidence is also on the rise,even among premenopausal women. Acting through systemic and local influences, obesity could be viewed as a potential driving force for breast cancer development; however, this relationship seems rather complex. Accumulating evidence indicates that obesity decreasesthe incidence of breast cancer but increases rates of mortality,metastasis and therapeutic resistance in premenopausal women. We aim to provide an in-depth insight into the molecular mechanisms underlying the intriguing relationship between breast cancer and obesity by focusing on cross-examinationof metabolic alterations in breast cancer and cancer-associated adipose tissue. Metabolic reprogramming will be discussed through the potential influences obesityexerts on major pathways in glucose, lipid, and mitochondrial metabolism in breast cancer and cancer-associated adipose tissue. An overview of the wide-ranging implications of context-dependent metabolic reprogramming for personalized diagnostic and therapeutic approaches will be given.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia",
title = "Molecular basis of obesity and cancer",
pages = "55-55",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4681"
}

Kalezić, A., Udicki, M., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2021). Molecular basis of obesity and cancer. in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia
Belgrade: Serbian Nutrition Society., 55-55.
https://hdl.handle.net/21.15107/rcub_ibiss_4681

Kalezić A, Udicki M, Srdić Galić B, Korać A, Janković A, Korać B. Molecular basis of obesity and cancer. in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia. 2021;:55-55.
https://hdl.handle.net/21.15107/rcub_ibiss_4681 .

Kalezić, Anđelika, Udicki, Mirjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Molecular basis of obesity and cancer" in 14th International Congress on Nutrition: A Place Where Science Meets Practice, Book of Abstracts; 2021 Nov 8-10; Belgrade, Serbia (2021):55-55,
https://hdl.handle.net/21.15107/rcub_ibiss_4681 .

TY  - JOUR
AU  - Kalezić, Anđelika
AU  - Udicki, Mirjana
AU  - Srdić Galić, Biljana
AU  - Aleksić, Marija
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2020
UR  - https://www.mdpi.com/1422-0067/21/24/9676
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4082
AB  - Metabolic reprogramming that favors high glycolytic flux with lactate production in normoxia is among cancer hallmarks. Lactate is an essential oncometabolite regulating cellular redox homeostasis, energy substrate partitioning, and intracellular signaling. Moreover, malignant phenotype’s chief characteristics are dependent on the interaction between cancer cells and their microenvironment. In breast cancer, mammary adipocytes represent an essential cellular component of the tumor milieu. We analyzed lactate concentration, lactate dehydrogenase (LDH) activity, and isozyme pattern, and LDHA/LDHB protein expression and tissue localization in paired biopsies of breast cancer tissue and cancer-associated adipose tissue in normal-weight and overweight/obese premenopausal women, compared to benign breast tumor tissue and adipose tissue in normal-weight and overweight/obese premenopausal women. We show that higher lactate concentration in cancer tissue is concomitant with a shift in isozyme pattern towards the “muscle-type” LDH and corresponding LDHA and LDHB protein expression changes. In contrast, significantly higher LDH activity in cancer-associated adipose tissue seems to be directed towards lactate oxidation. Moreover, localization patterns of LDH isoforms varied substantially across different areas of breast cancer tissue. Invasive front of the tumor showed cell-specific protein localization of LDHA in breast cancer cells and LDHB in cancer-associated adipocytes. The results suggest a specific, lactate-centric relationship between cancer tissue and cancer-associated adipose tissue and indicate how cancer-adipose tissue cross-talk may be influenced by obesity in premenopausal women.
PB  - MDPI AG
T2  - International Journal of Molecular Sciences
T1  - Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity
IS  - 24
VL  - 21
DO  - 10.3390/ijms21249676
SP  - 9676
ER  - 

@article{
author = "Kalezić, Anđelika and Udicki, Mirjana and Srdić Galić, Biljana and Aleksić, Marija and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2020",
abstract = "Metabolic reprogramming that favors high glycolytic flux with lactate production in normoxia is among cancer hallmarks. Lactate is an essential oncometabolite regulating cellular redox homeostasis, energy substrate partitioning, and intracellular signaling. Moreover, malignant phenotype’s chief characteristics are dependent on the interaction between cancer cells and their microenvironment. In breast cancer, mammary adipocytes represent an essential cellular component of the tumor milieu. We analyzed lactate concentration, lactate dehydrogenase (LDH) activity, and isozyme pattern, and LDHA/LDHB protein expression and tissue localization in paired biopsies of breast cancer tissue and cancer-associated adipose tissue in normal-weight and overweight/obese premenopausal women, compared to benign breast tumor tissue and adipose tissue in normal-weight and overweight/obese premenopausal women. We show that higher lactate concentration in cancer tissue is concomitant with a shift in isozyme pattern towards the “muscle-type” LDH and corresponding LDHA and LDHB protein expression changes. In contrast, significantly higher LDH activity in cancer-associated adipose tissue seems to be directed towards lactate oxidation. Moreover, localization patterns of LDH isoforms varied substantially across different areas of breast cancer tissue. Invasive front of the tumor showed cell-specific protein localization of LDHA in breast cancer cells and LDHB in cancer-associated adipocytes. The results suggest a specific, lactate-centric relationship between cancer tissue and cancer-associated adipose tissue and indicate how cancer-adipose tissue cross-talk may be influenced by obesity in premenopausal women.",
publisher = "MDPI AG",
journal = "International Journal of Molecular Sciences",
title = "Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity",
number = "24",
volume = "21",
doi = "10.3390/ijms21249676",
pages = "9676"
}

Kalezić, A., Udicki, M., Srdić Galić, B., Aleksić, M., Korać, A., Janković, A.,& Korać, B.. (2020). Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity. in International Journal of Molecular Sciences
MDPI AG., 21(24), 9676.
https://doi.org/10.3390/ijms21249676

Kalezić A, Udicki M, Srdić Galić B, Aleksić M, Korać A, Janković A, Korać B. Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity. in International Journal of Molecular Sciences. 2020;21(24):9676.
doi:10.3390/ijms21249676 .

Kalezić, Anđelika, Udicki, Mirjana, Srdić Galić, Biljana, Aleksić, Marija, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Lactate Metabolism in Breast Cancer Microenvironment: Contribution Focused on Associated Adipose Tissue and Obesity" in International Journal of Molecular Sciences, 21, no. 24 (2020):9676,
https://doi.org/10.3390/ijms21249676 . .