The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium
Altered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer cells have a unique ability to reprogram their metabolism by deviating their reliance from primarily oxidative phosphorylation (OXPHOS) to glycolysis, in order to support their survival. This metabol...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2024-03-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903099 |
| _version_ | 1827304506974535680 |
|---|---|
| author | Erna Mitaishvili Hanna Feinsod Zachary David Jessica Shpigel Chelsea Fernandez Moira Sauane Columba de la Parra |
| author_facet | Erna Mitaishvili Hanna Feinsod Zachary David Jessica Shpigel Chelsea Fernandez Moira Sauane Columba de la Parra |
| author_sort | Erna Mitaishvili |
| collection | DOAJ |
| description | Altered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer cells have a unique ability to reprogram their metabolism by deviating their reliance from primarily oxidative phosphorylation (OXPHOS) to glycolysis, in order to support their survival. This metabolic phenotype is referred to as the “Warburg effect” and is associated with an increase in glucose uptake, and a diversion of glycolytic intermediates to alternative pathways that support anabolic processes. These processes include synthesis of nucleic acids, lipids, and proteins, necessary for the rapidly dividing cancer cells, sustaining their growth, proliferation, and capacity for successful metastasis. Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with the poorest patient outcome due to its high rate of metastasis. TNBC is characterized by elevated glycolysis and in certain instances, low OXPHOS. This metabolic dysregulation is linked to chemotherapeutic resistance in TNBC research models and patient samples. There is more than a single mechanism by which this metabolic switch occurs and here, we review the current knowledge of relevant molecular mechanisms involved in advanced breast cancer metabolism, focusing on TNBC. These mechanisms include the Warburg effect, glycolytic adaptations, microRNA regulation, mitochondrial involvement, mitochondrial calcium signaling, and a more recent player in metabolic regulation, JAK/STAT signaling. In addition, we explore some of the drugs and compounds targeting cancer metabolic reprogramming. Research on these mechanisms is highly promising and could ultimately offer new opportunities for the development of innovative therapies to treat advanced breast cancer characterized by dysregulated metabolism. |
| first_indexed | 2024-04-24T17:38:05Z |
| format | Article |
| id | doaj.art-066b41ab322d42e2b36f720dc8cf2209 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-04-24T17:38:05Z |
| publishDate | 2024-03-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-066b41ab322d42e2b36f720dc8cf22092024-03-28T02:27:55ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-03-012939910.31083/j.fbl2903099S2768-6701(24)01242-5The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and CalciumErna Mitaishvili0Hanna Feinsod1Zachary David2Jessica Shpigel3Chelsea Fernandez4Moira Sauane5Columba de la Parra6Department of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USADepartment of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USADepartment of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USADepartment of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USADepartment of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USAPhD Program in Biology, The Graduate Center, City University of New York, New York, NY 10016, USADepartment of Chemistry, Herbert H. Lehman College, City University of New York, New York, NY 10468, USAAltered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer cells have a unique ability to reprogram their metabolism by deviating their reliance from primarily oxidative phosphorylation (OXPHOS) to glycolysis, in order to support their survival. This metabolic phenotype is referred to as the “Warburg effect” and is associated with an increase in glucose uptake, and a diversion of glycolytic intermediates to alternative pathways that support anabolic processes. These processes include synthesis of nucleic acids, lipids, and proteins, necessary for the rapidly dividing cancer cells, sustaining their growth, proliferation, and capacity for successful metastasis. Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with the poorest patient outcome due to its high rate of metastasis. TNBC is characterized by elevated glycolysis and in certain instances, low OXPHOS. This metabolic dysregulation is linked to chemotherapeutic resistance in TNBC research models and patient samples. There is more than a single mechanism by which this metabolic switch occurs and here, we review the current knowledge of relevant molecular mechanisms involved in advanced breast cancer metabolism, focusing on TNBC. These mechanisms include the Warburg effect, glycolytic adaptations, microRNA regulation, mitochondrial involvement, mitochondrial calcium signaling, and a more recent player in metabolic regulation, JAK/STAT signaling. In addition, we explore some of the drugs and compounds targeting cancer metabolic reprogramming. Research on these mechanisms is highly promising and could ultimately offer new opportunities for the development of innovative therapies to treat advanced breast cancer characterized by dysregulated metabolism.https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903099tnbcwarburg effectmetabolic reprogrammingglycolysishexokinaseoxphosmitochondrial ca2+rosjak/statmirnas |
| spellingShingle | Erna Mitaishvili Hanna Feinsod Zachary David Jessica Shpigel Chelsea Fernandez Moira Sauane Columba de la Parra The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium Frontiers in Bioscience-Landmark tnbc warburg effect metabolic reprogramming glycolysis hexokinase oxphos mitochondrial ca2+ ros jak/stat mirnas |
| title | The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium |
| title_full | The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium |
| title_fullStr | The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium |
| title_full_unstemmed | The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium |
| title_short | The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium |
| title_sort | molecular mechanisms behind advanced breast cancer metabolism warburg effect oxphos and calcium |
| topic | tnbc warburg effect metabolic reprogramming glycolysis hexokinase oxphos mitochondrial ca2+ ros jak/stat mirnas |
| url | https://www.imrpress.com/journal/FBL/29/3/10.31083/j.fbl2903099 |
| work_keys_str_mv | AT ernamitaishvili themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT hannafeinsod themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT zacharydavid themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT jessicashpigel themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT chelseafernandez themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT moirasauane themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT columbadelaparra themolecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT ernamitaishvili molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT hannafeinsod molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT zacharydavid molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT jessicashpigel molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT chelseafernandez molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT moirasauane molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium AT columbadelaparra molecularmechanismsbehindadvancedbreastcancermetabolismwarburgeffectoxphosandcalcium |