The role of lipids in cancer progression and metastasis

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1675 - 1699

Published: Oct. 18, 2022

Language: Английский

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CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(6)

Published: April 19, 2022

CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both signaling responding to DAMPs PAMPs, well long chain free fatty acid transporter. Recent studies have indicated that can integrate metabolic pathways through its dual thereby influence differentiation activation, ultimately help determine fate. Its expression along with innate adaptive cells contribute pathogenesis of common diseases, including atherosclerosis tumor progression, which makes downstream effectors potential therapeutic targets. This review comprehensively examines the variety cells, especially macrophages T We also briefly discuss function such adipocytes platelets, impact system via intercellular communication. Finally, outstanding questions this field are provided for directions future studies.

Language: Английский

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Obesity, Type 2 Diabetes, and Cancer Risk

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 10

Published: Feb. 2, 2021

Obesity and type 2 diabetes have both been associated with increased cancer risk are becoming increasingly prevalent. Metabolic abnormalities such as insulin resistance dyslipidemia obesity implicated in the obesity-cancer relationship. Multiple mechanisms proposed to link progression, including an increase insulin/IGF-1 signaling, lipid glucose uptake metabolism, alterations profile of cytokines, chemokines, adipokines, well changes adipose tissue directly adjacent sites. This review aims summarize provide update on epidemiological mechanistic evidence linking cancer, focusing roles insulin, lipids, tissue.

Language: Английский

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Contradictory roles of lipid metabolism in immune response within the tumor microenvironment

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Nov. 6, 2021

Complex interactions between the immune system and tumor cells exist throughout initiation development of cancer. Although eliminates malignantly transformed in early stage, surviving evade host defense through various methods even reprogram anti-tumor response to a pro-tumor phenotype obtain unlimited growth metastasis. The high proliferation rate increases demand for local nutrients oxygen. Poorly organized vessels can barely satisfy this requirement, which results an acidic, hypoxic, glucose-deficient microenvironment. As result, lipids microenvironment are activated utilized as primary source energy critical regulators both related cells. However, exact role lipid metabolism reprogramming remains unclear. A comprehensive understanding dysfunction its dual effects on is mapping detailed landscape immunology developing specific treatments cancer patients. In review, we have focused dysregulation discussed contradictory roles response. addition, summarized current therapeutic strategies targeting immunotherapy. This review provides summary

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 12, 2023

Abstract Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen nutrients, tumor cells undergo transformations exploit various ways acquiring lipid increasing oxidation. addition, stromal immune the microenvironment also reprogramming, which further affects functional phenotypes responses. Given metabolism plays a critical role supporting cancer progression remodeling microenvironment, targeting pathway could provide novel approach treatment. This review seeks to: (1) clarify overall landscape mechanisms cancer, (2) summarize landscapes within their roles progression, (3) potential therapeutic targets for metabolism, highlight combining such approaches with other anti-tumor therapies new opportunities patients.

Language: Английский

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Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance

Oncogenesis, Journal Year: 2022, Volume and Issue: 11(1)

Published: Aug. 9, 2022

Abstract Lipids are essential constituents for malignant tumors, as they absolutely required tumor growth and dissemination. Provided by the microenvironment (TME) or cancer cells themselves through activation of de novo synthesis pathways, orchestrate a large variety pro-tumorigenic functions. Importantly, TME cells, especially immune cancer-associated fibroblasts (CAFs) adipocytes (CAAs), also prone to changes in their lipid content, which hinder promote aggressiveness. In this review, we address significant findings contribution progression towards metastatic disease poor response therapeutic treatments. We highlight benefits targeting pathways preclinical models slow down metastasis development overcome chemo-and immunotherapy resistance.

Language: Английский

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Lipid-associated macrophages in the tumor-adipose microenvironment facilitate breast cancer progression

OncoImmunology, Journal Year: 2022, Volume and Issue: 11(1)

Published: June 8, 2022

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are most abundant immune cell type within TAME, although their diversity in TAME not clear. We first reveal infiltration M2-like macrophages associated with poor survival breast cancer. To explore lipid-associated alterations we also detected levels FFAs transporters including acid binding proteins (FABPs) and transport protein 1 (FATP1). results indicated expression tightly linked to function predicts impact on macrophages, performed single-cell RNA sequencing (scRNA-seq) spatial transcriptomics. Consequently, identified special subpopulation defined (LAMs), highly expressed macrophage markers (CD163, SPP1 C1QC), genes involved metabolism (FABP3, FABP4, FABP5, LPL LIPA) some receptors (LGALS3 TREM2). Functionally, LAMs were canonical functional signature accumulation enhancing phagocytosis, they mostly distributed junctional regions. Finally, allograft cancer mouse models confirmed depletion synergizes antitumorigenic effects anti-PD1 therapy. In summary, novel subtype has unique features clinical outcomes.

Language: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Language: Английский

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Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 31, 2022

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition therapy resistance via strengthened lipid synthesis, storage, catabolism. Breast cancer is strongly associated with the biological function of fatty owing abundant presence adipocytes breast tissue. It unraveled that tumor cells exhibit considerable plasticity based on metabolism, responding extra-tumoral a range metabolic signals, which microenvironment plays pivotal role. However, prognostic significance remains be further investigated. Alongside these insights, we retrieved 269 reliable metabolism-related genes (FMGs) identified landscape copy number variations expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis The Cancer Genome Atlas (TCGA) Molecular Taxonomy International Consortium (METABRIC) databases. Subsequently, signature 6 survival (OS)-related was generated using Lasso TCGA dataset validated two external cohorts. correlation between several essential clinical parameters, including T, N, PAM50 subtypes, unveiled comparing accumulating value various degrees. Furthermore, an optimal nomogram incorporating signature, age, American Joint Committee (AJCC) stage constructed, discrimination verified C-index, calibration curve, decision curve analysis. underlying implications for immune checkpoints inhibitors, microenvironment, predictive diverse strategies depicted ultimately. In conclusion, our findings indicate potential connotation cancer, supporting novel insights into patients' prognosis administrating effective immunotherapy.

Language: Английский

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