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Article

Continuous Inflammatory Stimulation Leads via Metabolic Plasticity to a Prometastatic Phenotype in Triple-Negative Breast Cancer Cells

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Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
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Blavatnik Center for Drug Discovery, Tel Aviv University, Tel Aviv 6997801, Israel
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Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel
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Author to whom correspondence should be addressed.
Academic Editor: Ira-Ida Skvortsova
Cells 2021, 10(6), 1356; https://doi.org/10.3390/cells10061356
Received: 30 March 2021 / Revised: 23 May 2021 / Accepted: 28 May 2021 / Published: 31 May 2021
(This article belongs to the Special Issue Cancer Stem Cells (CSC))
Chronic inflammation promotes cancer progression by affecting the tumor cells and their microenvironment. Here, we demonstrate that a continuous stimulation (~6 weeks) of triple-negative breast tumor cells (TNBC) by the proinflammatory cytokines tumor necrosis factor α (TNFα) + interleukin 1β (IL-1β) changed the expression of hundreds of genes, skewing the cells towards a proinflammatory phenotype. While not affecting stemness, the continuous TNFα + IL-1β stimulation has increased tumor cell dispersion and has induced a hybrid metabolic phenotype in TNBC cells; this phenotype was indicated by a transcription-independent elevation in glycolytic activity and by increased mitochondrial respiratory potential (OXPHOS) of TNBC cells, accompanied by elevated transcription of mitochondria-encoded OXPHOS genes and of active mitochondria area. The continuous TNFα + IL-1β stimulation has promoted in a glycolysis-dependent manner the activation of p65 (NF-κB), and the transcription and protein expression of the prometastatic and proinflammatory mediators sICAM-1, CCL2, CXCL8 and CXCL1. Moreover, when TNBC cells were stimulated continuously by TNFα + IL-1β in the presence of a glycolysis inhibitor, their conditioned media had reduced ability to recruit monocytes and neutrophils in vivo. Such inflammation-induced metabolic plasticity, which promotes prometastatic cascades in TNBC, may have important clinical implications in treatment of TNBC patients. View Full-Text
Keywords: glycolysis; inflammation; interleukin 1β; leukocyte migration; metabolism; oxidative phosphorylation; triple-negative breast cancer; tumor necrosis factor α glycolysis; inflammation; interleukin 1β; leukocyte migration; metabolism; oxidative phosphorylation; triple-negative breast cancer; tumor necrosis factor α
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MDPI and ACS Style

Morein, D.; Rubinstein-Achiasaf, L.; Brayer, H.; Dorot, O.; Pichinuk, E.; Ben-Yaakov, H.; Meshel, T.; Pasmanik-Chor, M.; Ben-Baruch, A. Continuous Inflammatory Stimulation Leads via Metabolic Plasticity to a Prometastatic Phenotype in Triple-Negative Breast Cancer Cells. Cells 2021, 10, 1356. https://doi.org/10.3390/cells10061356

AMA Style

Morein D, Rubinstein-Achiasaf L, Brayer H, Dorot O, Pichinuk E, Ben-Yaakov H, Meshel T, Pasmanik-Chor M, Ben-Baruch A. Continuous Inflammatory Stimulation Leads via Metabolic Plasticity to a Prometastatic Phenotype in Triple-Negative Breast Cancer Cells. Cells. 2021; 10(6):1356. https://doi.org/10.3390/cells10061356

Chicago/Turabian Style

Morein, Dina, Linor Rubinstein-Achiasaf, Hadar Brayer, Orly Dorot, Edward Pichinuk, Hagar Ben-Yaakov, Tsipi Meshel, Metsada Pasmanik-Chor, and Adit Ben-Baruch. 2021. "Continuous Inflammatory Stimulation Leads via Metabolic Plasticity to a Prometastatic Phenotype in Triple-Negative Breast Cancer Cells" Cells 10, no. 6: 1356. https://doi.org/10.3390/cells10061356

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