A loop involving NRF2, miR‐29b‐1‐5p and AKT, regulates cell fate of MDA‐MB‐231 triple‐negative breast cancer cells

Blasio, Anna De; Fiore, Riccardo Di; Pratelli, Giovanni; Drago-Ferrante, Rosa; Saliba, Christian; Baldacchino, Shawn; Grech, Godfrey; Scerri, Christian; Vento, Renza; Tesoriere, Giovanni

doi:10.1002/jcp.29062

Cited by 37 publications

(28 citation statements)

References 25 publications

(41 reference statements)

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“…In TNBC cells, NRF2silencing can suppress HIF-1α enrichment and sequentially lower expression of glycolysis enzymes. Specifically, dysregulated HIF-1α signaling in NRF2-silenced TNBC cells is induced by miR-181c, indicating that NRF2 and miR-181c may be novel targets for blocking HIF-1α-mediated glycolytic adaption in TNBC cells (58). C-myc is another oncogenic transcriptional factor regulating the glycolytic phenotype of TNBC tumors.…”

Section: Glycolysismentioning

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: Glycolysismentioning

confidence: 99%

Metabolic Reprogramming in Triple-Negative Breast Cancer

et al. 2020

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“…High expression of glycolysis-related enzymes, such as HK2 ( Jiang S. et al, 2012 ), PKM2 ( Christofk et al, 2008 ; Ma et al, 2019 ), and LDH ( McCleland et al, 2012 ; Huang et al, 2016 ; Dong et al, 2017 ), and that of lactate transporters MCT1 and MCT4 have also been reported in TNBC ( Pinheiro et al, 2010 ; McCleland et al, 2012 ; Doyen et al, 2014 ). The high expression of glycolysis-related proteins in TNBC is owing to the fact that the glycolysis regulatory factors, such as HIF-1 ( Lin et al, 2016 ; De Blasio et al, 2020 ), c-myc ( Palaskas et al, 2011 ; Shen et al, 2015 ), and EGF signaling ( Avanzato et al, 2018 ), are promoted in TNBC. Therefore, TNBC cells are much more dependent on glucose metabolism than non-TNBC cells (MCF-7) ( Robey et al, 2005 ), and GLUT1 inhibition shows a more anti-proliferative effect for TNBC cells than non-TNBC cells (MCF-7) ( Yang et al, 2021 ).…”

Section: Glucose Metabolism and Glycolysis-related Metabolic Pathways In Breast Cancermentioning

confidence: 99%

Glucose Metabolism and Glucose Transporters in Breast Cancer

Shin

Koo

2021

Front. Cell Dev. Biol.

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Breast cancer is the most common malignancy in women worldwide and is associated with high mortality rates despite the continuously advancing treatment strategies. Glucose is essential for cancer cell metabolism owing to the Warburg effect. During the process of glucose metabolism, various glycolytic metabolites, such as serine and glycine metabolites, are produced and other metabolic pathways, such as the pentose phosphate pathway (PPP), are associated with the process. Glucose is transported into the cell by glucose transporters, such as GLUT. Breast cancer shows high expressions of glucose metabolism-related enzymes and GLUT, which are also related to breast cancer prognosis. Triple negative breast cancer (TNBC), which is a high-grade breast cancer, is especially dependent on glucose metabolism. Breast cancer also harbors various stromal cells such as cancer-associated fibroblasts and immune cells as tumor microenvironment, and there exists a metabolic interaction between these stromal cells and breast cancer cells as explained by the reverse Warburg effect. Breast cancer is heterogeneous, and, consequently, its metabolic status is also diverse, which is especially affected by the molecular subtype, progression stage, and metastatic site. In this review, we will focus on glucose metabolism and glucose transporters in breast cancer, and we will additionally discuss their potential applications as cancer imaging tracers and treatment targets.

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“…Nrf2 is known to protect normal cells from oxidative stress and inflammation-induced cellular damage. Unfortunately, the elevated Nrf2 also protects cancer cells from chemotherapeutic- and radiation-induced damage [ 21 , 22 , 23 ]. Nrf2-regulated antioxidant response was suggested to play a crucial role in controlling BC cell survival [ 24 ] and development of drug resistance [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

et al. 2021

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Nuclear factor erythroid-2 related factor-2 (Nrf2) is an oxidative stress-response transcriptional activator that promotes carcinogenesis through metabolic reprogramming, tumor promoting inflammation, and therapeutic resistance. However, the extension of Nrf2 expression and its involvement in regulation of breast cancer (BC) responses to chemotherapy remain largely unclear. This study determined the expression of Nrf2 in BC tissues (n = 46) and cell lines (MDA-MB-453, MCF-7, MDA-MB-231, MDA-MB-468) with diverse phenotypes. Immunohistochemical (IHC)analysis indicated lower Nrf2 expression in normal breast tissues, compared to BC samples, although the difference was not found to be significant. However, pharmacological inhibition and siRNA-induced downregulation of Nrf2 were marked by decreased activity of NADPH quinone oxidoreductase 1 (NQO1), a direct target of Nrf2. Silenced or inhibited Nrf2 signaling resulted in reduced BC proliferation and migration, cell cycle arrest, activation of apoptosis, and sensitization of BC cells to cisplatin in vitro. Ehrlich Ascites Carcinoma (EAC) cells demonstrated elevated levels of Nrf2 and were further tested in experimental mouse models in vivo. Intraperitoneal administration of pharmacological Nrf2 inhibitor brusatol slowed tumor cell growth . Brusatol increased lymphocyte trafficking towards engrafted tumor tissue in vivo, suggesting activation of anti-cancer effects in tumor microenvironment. Further large-scale BC testing is needed to confirm Nrf2 marker and therapeutic capacities for chemo sensitization in drug resistant and advanced tumors.

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A loop involving NRF2, miR‐29b‐1‐5p and AKT, regulates cell fate of MDA‐MB‐231 triple‐negative breast cancer cells

Cited by 37 publications

References 25 publications

Metabolic Reprogramming in Triple-Negative Breast Cancer

Metabolic Reprogramming in Triple-Negative Breast Cancer

Glucose Metabolism and Glucose Transporters in Breast Cancer

Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo

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