The rate of aerobic glycolysis is a pivotal regulator of tumor progression

Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Hemmati, Shahrooz; Mansouri, Kamran; Vaisi‐Raygani, Asad

doi:10.1007/s40200-021-00774-7

Cited by 6 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CM collected from BC cell cultures were characterized by varying contents of glucose and lactate, reflecting the different glycolytic activity of the two BC cell lines and its modulation by hypoxia. Glucose depletion and lactate enrichment were especially prominent in CM-MDA, indicating that MDA-MB-231 cells were more glycolytic than MCF-7 cells, in agreement with previous reports [33][34][35][36]. Tumor-derived lactate is known to critically influence both innate and adaptive immunity in the TME [37].…”

Section: Discussionsupporting

confidence: 90%

Metabolic Reprogramming of Breast Tumor-Educated Macrophages Revealed by NMR Metabolomics

Almeida

Helguero

Duarte

2023

Cancers

View full text Add to dashboard Cite

The metabolic crosstalk between tumor cells and tumor-associated macrophages (TAMs) has emerged as a critical contributor to tumor development and progression. In breast cancer (BC), the abundance of immune-suppressive TAMs positively correlates with poor prognosis. However, little is known about how TAMs reprogram their metabolism in the BC microenvironment. In this work, we have assessed the metabolic and phenotypic impact of incubating THP-1-derived macrophages in conditioned media (CM) from two BC cell lines cultured in normoxia/hypoxia: MDA-MB-231 cells (highly metastatic, triple-negative BC), and MCF-7 cells (less aggressive, luminal BC). The resulting tumor-educated macrophages (TEM) displayed prominent differences in their metabolic activity and composition, compared to control cells (M0), as assessed by exo- and endometabolomics. In particular, TEM turned to the utilization of extracellular pyruvate, alanine, and branched chain keto acids (BCKA), while exhibiting alterations in metabolites associated with several intracellular pathways, including polyamines catabolism (MDA-TEM), collagen degradation (mainly MCF-TEM), adenosine accumulation (mainly MDA-TEM) and lipid metabolism. Interestingly, following a second-stage incubation in fresh RPMI medium, TEM still displayed several metabolic differences compared to M0, indicating persistent reprogramming. Overall, this work provided new insights into the metabolic plasticity of TEM, revealing potentially important nutritional exchanges and immunoregulatory metabolites in the BC TME.

show abstract

Section: Discussionsupporting

confidence: 90%

Metabolic Reprogramming of Breast Tumor-Educated Macrophages Revealed by NMR Metabolomics

Almeida

Helguero

Duarte

2023

Cancers

View full text Add to dashboard Cite

show abstract

“…MCF-7 cells displayed higher glucose consumption, lactate secretion, and higher intracellular lactate levels (in the case of HT-treated cells), indicating an increase in glycolytic flux. According to our own results and the data of others [34][35][36], in basal conditions, MCF-7 cells tend to be less glycolytic than MDA-MB-231 cells, which may partially justify their differential regulation of glycolysis upon treatment with the phenols. A few other studies have also reported phenolic compounds such as Gossypol or Catechin to stimulate glucose uptake by MCF-7 cells [37,38], which is a response that may be viewed as an adaptive mechanism to oxidative stress [39].…”

Section: Discussionsupporting

confidence: 70%

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin

et al. 2023

View full text Add to dashboard Cite

The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.

show abstract

“…Glycolysis can lead to an increase in HIF-1a levels, which in turn raises VEGF expression (121). Aerobic glycolysis stimulates angiogenesis by producing lactate, which acidifies the extracellular environment and enhances VEGF expression (122).…”

Section: Glucose Metabolismmentioning

confidence: 99%

Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment

Zhi,

Chen,

Huang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Globally, breast cancer stands as the most prevalent form of cancer among women. The tumor microenvironment of breast cancer often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in breast cancer, playing a pivotal role in the anoxic microenvironment by mediating a series of reactions. Hypoxia-inducible factor 1-alpha is involved in regulating downstream pathways and target genes, which are crucial in hypoxic conditions, including glycolysis, angiogenesis, and metastasis. These processes significantly contribute to breast cancer progression by managing cancer-related activities linked to tumor invasion, metastasis, immune evasion, and drug resistance, resulting in poor prognosis for patients. Consequently, there is a significant interest in Hypoxia-inducible factor 1-alpha as a potential target for cancer therapy. Presently, research on drugs targeting Hypoxia-inducible factor 1-alpha is predominantly in the preclinical phase, highlighting the need for an in-depth understanding of HIF-1α and its regulatory pathway. It is anticipated that the future will see the introduction of effective HIF-1α inhibitors into clinical trials, offering new hope for breast cancer patients. Therefore, this review focuses on the structure and function of HIF-1α, its role in advancing breast cancer, and strategies to combat HIF-1α-dependent drug resistance, underlining its therapeutic potential.

show abstract

The rate of aerobic glycolysis is a pivotal regulator of tumor progression

Cited by 6 publications

References 28 publications

Metabolic Reprogramming of Breast Tumor-Educated Macrophages Revealed by NMR Metabolomics

Metabolic Reprogramming of Breast Tumor-Educated Macrophages Revealed by NMR Metabolomics

Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin

Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment

Contact Info

Product

Resources

About