Glucose Metabolism and Glucose Transporters in Breast Cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Сен. 6, 2021

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

Язык: Английский

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Immature natural killer cells promote progression of triple-negative breast cancer

Science Translational Medicine, Год журнала: 2023, Номер 15(686)

Опубликована: Март 8, 2023

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and generally considered to be antitumorigenic. Using single-cell RNA sequencing functional analysis of multiple triple-negative breast cancer (TNBC) basal samples, we observed a unique subcluster Socs3 high CD11b − CD27 immature NK were present only in TNBC samples. These tumor-infiltrating expressed reduced granzyme signature and, mice, responsible for activating stem through Wnt signaling. cell–mediated activation these subsequently enhanced progression whereas depletion or ligand secretion from by LGK-974 decreased progression. In addition, cell inhibition their function improved anti–programmed death 1 (PD-L1) antibody chemotherapy response mice with TNBC. Furthermore, samples patients non-TNBC revealed increased numbers CD56 bright tumors correlated poor overall survival Together, our findings identify population protumorigenic may exploited both diagnostic therapeutic strategies improve outcomes

Язык: Английский

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LOX-1 and cancer: an indissoluble liaison

Cancer Gene Therapy, Год журнала: 2021, Номер 28(10-11), С. 1088 - 1098

Опубликована: Янв. 5, 2021

Recently, a strong correlation between metabolic disorders, tumor onset, and progression has been demonstrated, directing new therapeutic strategies on targets. OLR1 gene encodes the LOX-1 receptor protein, responsible for recognition, binding, internalization of ox-LDL. In past, several studied, aimed to clarify role in atherosclerosis, shed light its stimulation expression adhesion molecules, pro-inflammatory signaling pathways, pro-angiogenic proteins, including NF-kB VEGF, vascular endothelial cells macrophages. recent years, upregulation different tumors evidenced involvement cancer metastasis. this review, we outline spreading metastasis, evidencing function VEGF induction, HIF-1alpha activation, MMP-9/MMP-2 expression, pushing up neoangiogenic epithelial-mesenchymal transition process glioblastoma, osteosarcoma prostate, colon, breast, lung, pancreatic tumors. Moreover, our studies contributed evidence interacting with WNT/APC/β-catenin axis, highlighting pathways sporadic colon onset. The application volatilome analysis high expressing tumor-bearing mice correlates evolution, suggesting closed link changes individual volatile compounds thus providing viable method simple, non-invasive alternative monitoring progression. These findings underline as regulator progression, migration, invasion, metastasis formation, tumor-related neo-angiogenesis, proposing promising target enhancing current antineoplastic strategies.

Язык: Английский

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Exosomal EPHA2 derived from highly metastatic breast cancer cells promotes angiogenesis by activating the AMPK signaling pathway through Ephrin A1-EPHA2 forward signaling

Theranostics, Год журнала: 2022, Номер 12(9), С. 4127 - 4146

Опубликована: Янв. 1, 2022

Rationale: Angiogenesis is a fundamental process of tumorigenesis, growth, invasion and metastatic spread.Extracellular vesicles, especially exosomes, released by primary tumors promote angiogenesis cancer progression.However, the mechanism underlying pro-angiogenic potency cell-derived exosomes remains poorly understood.Methods: Exosomes were isolated from breast cells with high potential (HM) low (LM).The effects these evaluated in vitro tube formation assays, wound healing rat arterial ring budding assays vivo Matrigel plug assays.Subsequently, RNA sequencing, shRNA-mediated gene knockdown, overexpression different EPHA2 mutants, small-molecule inhibitors used to analyze angiogenesis-promoting effect exosomal its downstream mechanism.Finally, xenograft tumor models established using expressing levels mimic secretion vivo, metastasis monitored IVIS Spectrum imaging system Computed Tomography.Results: Herein, we demonstrated that produced HM can metastasis.EPHA2 was rich HM-derived conferred effect.Exosomal be transferred endothelial cells.Moreover, it stimulate migration tube-forming abilities vivo.Mechanistically, activates AMPK signaling via ligand Ephrin A1-dependent canonical forward pathway.Moreover, inhibition impairs EPHA2-mediated effects.Conclusion: Our findings identify novel intercellular communication microenvironment provoke metastasis.Targeting EPHA2-AMPK may serve as strategy for therapy.

Язык: Английский

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Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 156, С. 113861 - 113861

Опубликована: Окт. 10, 2022

Triple-negative breast cancer (TNBC) is a subtype of that highly aggressive and hypoxic compared with other subtypes. The role hypoxia inducible factor 1α (HIF-1α) as key transcription in oncogenic processes has been extensively studied. Recently, it shown HIF-1α regulates the complex biological TNBC, such glycolysis, angiogenesis, invasion metastasis, stem cells (BCSCs) enrichment, immune escape, to promote TNBC survival development through activation downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, signaling regulatory networks, epigenetic regulators are involved upstream expression HIF-1α. However, further studies needed determine potential future directions targeting TNBC. This article discusses We also explored mechanism by which drives progression. significance for immunotherapy, chemotherapy, anti-angiogenic therapy, photodynamic therapy discussed. intrinsic mechanism, existing problems

Язык: Английский

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Glutamine transporter SLC38A3 promotes breast cancer metastasis via Gsk3β/β-catenin/EMT pathway

Cancer Letters, Год журнала: 2024, Номер 586, С. 216653 - 216653

Опубликована: Фев. 2, 2024

Язык: Английский

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Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Май 8, 2024

Objective The established link between posttranslational modifications of histone and non-histone lysine (K) residues in cell metabolism, their role cancer progression, is well-documented. However, the lactylation expression signature triple-negative breast (TNBC) remains underexplored. Methods We conducted a comprehensive lactylproteome profiling eight pairs TNBC samples matched adjacent tissues. This was achieved through 4-Dimensional label-free quantitative proteomics combined with analysis (4D-LFQP-LA). identified lactylated proteins detected using immunoblotting immunohistochemistry (IHC) specific primary antibodies, clinicopathological prognostic significance evaluated. Results Our 58 sites on 48 proteins, delineating protein alteration TNBC. Bioinformatic functional analyses indicated that these play crucial roles regulating key biological processes Notably, at position 12 (H4K12lac) H4 domain found to be upregulated Further investigations showed high prevalence H4K12lac upregulation TNBC, positive rates 93.19% (137/147) 92.93% (92/99) tissue chip validation cohorts, respectively. correlated positively Ki-67 inversely overall survival (OS) (HR [hazard ratio] =2.813, 95%CI [credibility interval]: 1.242-6.371, P =0.0164), suggesting its potential as an independent marker (HR=3.477, 95%CI: 1.324-9.130, =0.011). Conclusions Lactylation significant post-translational modification proteins. emerges promising biomarker for offering insights into profiles linking clinical implications

Язык: Английский

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The Molecular Mechanisms behind Advanced Breast Cancer Metabolism: Warburg Effect, OXPHOS, and Calcium

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(3)

Опубликована: Март 13, 2024

Altered metabolism represents a fundamental difference between cancer cells and normal cells. Cancer have unique ability to reprogram their by deviating reliance from primarily oxidative phosphorylation (OXPHOS) glycolysis, in order support survival. This metabolic phenotype is referred as the “Warburg effect” associated with an increase glucose uptake, diversion of glycolytic intermediates alternative pathways that anabolic processes. These processes include synthesis nucleic acids, lipids, proteins, necessary for rapidly dividing cells, sustaining growth, proliferation, capacity successful metastasis. Triple-negative breast (TNBC) one most aggressive subtypes cancer, poorest patient outcome due its high rate TNBC characterized elevated glycolysis certain instances, low OXPHOS. dysregulation linked chemotherapeutic resistance research models samples. There more than single mechanism which this switch occurs here, we review current knowledge relevant molecular mechanisms involved advanced metabolism, focusing on TNBC. Warburg effect, adaptations, microRNA regulation, mitochondrial involvement, calcium signaling, recent player JAK/STAT signaling. In addition, explore some drugs compounds targeting reprogramming. Research these highly promising could ultimately offer new opportunities development innovative therapies treat dysregulated metabolism.

Язык: Английский

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Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells

Metabolites, Год журнала: 2024, Номер 14(5), С. 249 - 249

Опубликована: Апрель 25, 2024

The metabolic reprogramming that promotes tumorigenesis in glioblastoma is induced by dynamic alterations the hypoxic tumor microenvironment, as well transcriptional and signaling networks, which result changes global genetic expression. pathways PI3K/AKT/mTOR RAS/RAF/MEK/ERK stimulate cell metabolism, either directly or indirectly, modulating factors p53, HIF1, c-Myc. overexpression of HIF1 c-Myc, master regulators cellular a key contributor to synthesis bioenergetic molecules mediate glioma transformation, proliferation, survival, migration, invasion modifying transcription levels gene groups involved metabolism. Meanwhile, tumor-suppressing protein negatively regulates often lost glioblastoma. Alterations this triad induce shift cells allows them adapt survive such mutations, hypoxia, acidosis, presence reactive oxygen species, nutrient deprivation, activity expression molecules, enzymes, metabolites, transporters, glycolysis glutamine pentose phosphate cycle, tricarboxylic acid oxidative phosphorylation, degradation fatty acids nucleic acids. This review summarizes our current knowledge on role p53 genic regulatory network for metabolism cells, potential therapeutic inhibitors these factors.

Язык: Английский

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Hypoxia‑induced SREBP1‑mediated lipogenesis and autophagy promote cell survival via fatty acid oxidation in breast cancer cells

Oncology Letters, Год журнала: 2025, Номер 29(4)

Опубликована: Фев. 7, 2025

In the hypoxic tumor microenvironment, cancer cells undergo metabolic reprogramming to survive. The present study aimed assess effects of conditions on lipid metabolism breast elucidate mechanisms by which survive in an unfavorable environment. Cell viability was assessed trypan blue staining, MTT and Annexin V‑PI assays. Intracellular levels were quantified using Nile red stain with immunofluorescence (IF). Autophagy detected LC3 antibody, Cyto‑ID stain, IF, Western blotting, flow cytometry. Fatty acid oxidation (FAO) ATP production analyzed specific assays, while gene expression reverse transcription‑polymerase chain reaction. siRNA transfection used for knockdown, Kaplan‑Meier analysis performed survival analysis. Fatostatin rapamycin served as inhibitor sterol regulatory element‑binding protein 1 (SREBP1) autophagy inducer, respectively. Under conditions, triple‑negative (TNBC) MDA‑MB‑231 showed markedly increased proliferation rates compared normal (MCF‑10A) estrogen receptor‑positive (MCF‑7), no change apoptosis. lipogenesis, FAO‑related enzymes activation SREBP1, a key transcription factor lipogenic genes, whereas these changes not observed MCF‑7 cells. When SREBP1 inhibited chemical inhibitors siRNA, lipogenic, autophagic decreased, resulting reduced cells; however, this effect restored when inducer added. demonstrated that higher patients TNBC associated worse prognosis, suggesting SREBP1‑mediated under hypoxia is essential cell survival. results indicate strategies targeting could be exploited treat improve prognosis.

Язык: Английский

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