Breast cancer metabolic cross-talk: Fibroblasts are hubs and breast cancer cells are gatherers of lipids

Lopes‐Coelho, Filipa; André, Saudade; Félix, Ana; Serpa, Jacinta

doi:10.1016/j.mce.2017.01.031

Cited by 69 publications

(62 citation statements)

References 39 publications

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“…Fibroblasts that have mutual effects on cancer cells are regarded as cancer-associated fibroblasts (CAFs). Several studies show CAF-conditioned medias increase TNBC cell proliferation (102)(103)(104)(105). Interestingly, CAFs can recycle tumor-derived lactate as a source of energy when cocultured with TNBC cells, sparing glucose to be utilized by adjacent tumor cells, to reinforce the glucose supply to TNBC cells.…”

Section: Metabolic Interaction With Cancer-associated Fibroblastsmentioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

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Section: Metabolic Interaction With Cancer-associated Fibroblastsmentioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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“…This interesting GS/GLS intercellular cycle within the TME deserves to be further explored. On the other hand, fatty acids are also synthetized and secreted by CAFs and taken up by breast tumor cells (Figure ), favoring tumor progression . Furthermore, NOS‐expressing CAFs support growth of breast and prostate cancer cells, suggesting the relevance of NO metabolism in these cells for tumor progression …”

Section: Implications Of Tumor and Accompanying Cells Metabolism For mentioning

confidence: 99%

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

Ocaña

Martínez‐Poveda

Quesada

et al. 2018

Medicinal Research Reviews

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Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME).Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the TME and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that TME is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with

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“…Research by several groups has verified such altered regulation in cancer, which leads to metabolic reprogramming [2]. This knowledge might reveal new targets to involve in cancer circulation, cancer cells use a pathway that allows an intracellular de novo lipid synthesis even if there is extracellular lipid supply [15,16]. It has been shown that fatty acids participate in cellular renewal and in mitogenesis, and that in cancer cells the de novo synthesis of fatty acids positively correlates with tumor aggressiveness [16].…”

Section: Introductionmentioning

confidence: 97%

“…This knowledge might reveal new targets to involve in cancer circulation, cancer cells use a pathway that allows an intracellular de novo lipid synthesis even if there is extracellular lipid supply [15,16]. It has been shown that fatty acids participate in cellular renewal and in mitogenesis, and that in cancer cells the de novo synthesis of fatty acids positively correlates with tumor aggressiveness [16]. In support of this finding, Antalis et al [17] have shown that aggressive breast cancer cells (MDA-MB-231 and MDA-MB-436) revealed higher levels of cytoplasmic lipids, whereas Slebe et al [18] associated tumor migration with the uptake of exogenous lipids.…”

Section: Introductionmentioning

confidence: 99%

Metabolism: A New Frontier in Cancer Research

Rodrigues¹

2017

JCPCR

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Submit Manuscript | http://medcraveonline.com development and can be used by the pharmaceutical industry to generate novel drugs. This is validated by the approval of Agas and Celgene's enasidenib by the FDA. This drug modulates the metabolism and is used as a medication against acute myelogenous leukemia. Enasidenib is an inhibitor of the mutated isocitrate dehydrogenase (IDH2), one of the main enzymes of the citric acid cycle (also known as Krebs cycle), a central pathway which converts molecules coming from all 3 main catabolic pathways into intermediate metabolites that finally fuel the respiratory chain, the main energy providing process in cells. IDH enzymes usually metabolize isocitrate into α-ketoglutarate, a crucial step in the citric cycle. When mutated in some cancers, this enzyme starts producing 2-hydroxyglutarate, a metabolite that causes cell differentiation defects and impairs histone demethylation [3]. While this approval highlights the promising role of anticancer drugs modulating metabolism, researchers have struggled to find other therapeutically useful targets in metabolic pathways. Tumor MetabolismCell metabolism as well as cancer development and growth is complex. The intermodulation between metabolic pathways and the plasticity of these routes, plus the capacity of tumor cells to adapt are factors that slow down the advances in their understanding. Factors such as poor oxygenation, acidity and deprivation of nutrients, which normally cause cell death, are rapidly converted into promoters by tumor cells [4,5].The reprogramming of the glucose metabolism is a good example for this flexibility. Tumor cells typically exhibit a high uptake of glucose and are mainly metabolizing anaerobically. For many years, the explanation for that was attributed to the lack of oxygen, once the proliferation rate of tumor exceeds the angiogenesis. However, Otto Warburg (1927) verified that even in the presence of oxygen, tumor cells prefer to metabolize glucose into lactic acid. This process is known as anaerobic glycolysis and has been extensively studied throughout the years, but is still poorly understood [6,7]. Recent studies demonstrated that tumor cells prefer the anaerobic metabolism because it more efficiently produces energy and basic metabolites for protein biosynthesis as compared to aerobic metabolism [8,9]. These findings were confirmed in a study showing that one of the main molecule that control glycolysis and the anaerobic metabolism, the glucosetransporter (GLUT), was up regulated in breast tumor cell lines [10].To corroborate the complexity of cancer metabolism, it has been shown recently that some tumors also use the mitochondrial oxidative phosphorylations [11,12]. Growing evidence of the importance of the glucose metabolism for tumor development and the need of new therapeutic targets, lead to the application of drugs inhibiting the glycolytic pathway as potential approach. Metformin for example, a drug already widely used in diabetes treatment, decreases glucose consumption and, conseque...

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Breast cancer metabolic cross-talk: Fibroblasts are hubs and breast cancer cells are gatherers of lipids

Cited by 69 publications

References 39 publications

Metabolic Reprogramming in Triple-Negative Breast Cancer

Metabolic Reprogramming in Triple-Negative Breast Cancer

Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target

Metabolism: A New Frontier in Cancer Research

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