Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis

Science Advances, Journal Year: 2024, Volume and Issue: 10(42)

Published: Oct. 16, 2024

A major therapeutic barrier in melanoma is the coexistence of diverse cellular states marked by distinct metabolic traits. Transitioning from a proliferative to an invasive phenotype coupled with increased ferroptosis vulnerability. However, regulatory circuits controlling susceptibility across cell are unknown. In this work, we identified Apolipoprotein E ( APOE ) as top lipid-metabolism gene segregating MITF high /AXL low proliferative/ferroptosis-resistant invasive/ferroptosis-sensitive state. Mechanistically, ApoE secreted cells protects ferroptosis-inducing agents reducing content peroxidation-prone polyunsaturated fatty acids and boosting GPX4 levels both vitro vivo. Whole-exome sequencing indicates that expression patients associated resistance ferroptosis, regardless germline status. aggregate, found ferroptosis-resistance mechanism between relying on potential biomarker for poor response melanoma.

Language: Английский

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Secretome and Proteome of Extracellular Vesicles Provide Protein Markers of Lung and Colorectal Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1016 - 1016

Published: Jan. 25, 2025

Colorectal cancer (CRC) and lung (LC) are leading causes of cancer-related mortality, highlighting the need for minimally invasive diagnostic, prognostic, predictive markers these cancers. Proteins secreted by a tumor into extracellular space directly, known as secretome, well proteins in extra-cellular vesicles (EVs), represent an attractive source biomarkers CRC LC. We performed proteomic analyses on secretome EV samples from LC (A549, NCI-H23, NCI-H460) (Caco2, HCT116, HT-29) cell lines targeted mass spectrometry EVs plasma 20 patients with 19 healthy controls. A total 782 were identified across samples. Of these, 22 44 protein significantly elevated samples, respectively. Functional annotation revealed enrichment linked to metastasis progression both types. In isolated CRC, ITGB3, HSPA8, TUBA4A, TLN1 reduced, whereas FN1, SERPINA1, CST3 elevated, compared These findings support development liquid biopsy methods detection, prognosis, treatment monitoring CRC.

Language: Английский

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Apolipoproteins in Psoriasis: The Effect of Acitretin Treatment and UVB Phototherapy

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 196 - 196

Published: March 12, 2025

Background: Psoriasis is a chronic, multi-system inflammatory disease frequently associated with metabolic syndrome and lipid disturbances. Apolipoproteins, as essential regulators of metabolism, may play critical role in these abnormalities, potentially influencing severity systemic inflammation. The aim this study was to compare serum concentrations chosen apolipoproteins patients psoriasis before after treatment acitretin or narrowband UVB (NB-UVB). Methods: This conducted on 39 psoriasis. concentration nine C-reactive protein quantified using the Bio-Plex Immunoassay Kit. Results: ApoA2, ApoC1, ApoD, ApoE, ApoJ were higher group compared NB-UVB treatment, while ApoA1/ApoA2 ratio lower. We also observed negative association between Area Severity Index (PASI) treatment. Conclusions: results confirm presence disturbances psoriatic patients. did not cause any significant changes profile. Thus, we found no detrimental impact profile, despite rise total cholesterol Further research needed explore whether specific therapeutic approaches can modify improve long-term cardiovascular outcomes population.

Language: Английский

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APOC1, transcriptionally regulated by FOXM1, promotes M2 macrophage polarization and cervical cancer progression

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Journal Year: 2025, Volume and Issue: 830, P. 111904 - 111904

Published: Jan. 1, 2025

Language: Английский

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ESCRT may function as a tumor biomarker, transitioning from pan-cancer analysis to validation within breast cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 31, 2025

Background Studies have shown that ESCRT genes affect cell aging, immune environment, and tumors. BRCA was used to explore its effects on tumor prognosis therapy. Methods The data sets of Cancer Genome Atlas (TCGA), Genome-Tissue Expression Plan (GTEX), Human Protein Mapping (HPA), Gene Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), R software package, bioinformatics methods were mine the potential carcinogenic ESCRT, including expression level, prognostic value, value in various types tissues, function family further verified breast cancer. Results showed significant differential cancers, such as bladder urothelial carcinoma liver, cervical, renal, esophageal, head, neck cancers ( P < 0.05). Abnormal is associated with poor adrenocortical carcinoma, cancer, cervical cancer level significantly infiltration modulation stromal/immune score (all Enrichment analysis immune-related functions transport signaling pathways cells. Moreover, serves an early diagnostic marker for several tumors prognosis. This confirms most immune-infiltrating cells pan-carcinomas. Taken together, these studies highlight importance gene VPS37D initiation, progression, response. Conclusion study highlights ESCRT’s detection via pan-cancer analysis, showing variations between normal role progression through microenvironment, specificity sensitivity detection. gene, variation predicts patient related suggesting a novel biomarker diagnosis assessment.

Language: Английский

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Delineating the intricacies of polymorphisms, structures, functions and therapeutic applications of biological high-density lipoprotein-apolipoprotein M: A review

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143187 - 143187

Published: April 1, 2025

Language: Английский

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Sesamin regulates breast cancer through reprogramming of lipid metabolism

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: April 15, 2025

Metabolic reprogramming is one of the hallmarks breast cancer (BC), involving elevated synthesis and uptake lipids, for catering to increased energy demand cells suppress host immune system. Besides promoting proliferation survival BC cells, lipid metabolism (LMR) associated with stemness chemoresistance. Recently, lignans have been reported their therapeutic potential against different cancers, including BC. Here, we explored target LMR pathways in through computational approach. Initially, 88 having anticancer activities, underwent druglikeness pharmacokinetics analysis, displaying promising pharmacokinetic properties, except 13 molecules violations. Molecular docking assessed interaction (NPACT) targets 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), Sterol regulatory element-binding proteins 1 2 (SREBP1 2), Low-density lipoprotein receptor (LDLR), Acetyl-CoA Acetyltransferase (ACAT1), ATP-binding cassette transporter (ABCA1), Liver X α (LXRα), Apolipoprotein A1 (APOA1), Fatty Acid Synthase (FASN), Peroxisome proliferator-activated gamma (PPARG), Stearoyl-CoA desaturase (SCD1), carboxylase (ACC1/ACACA, ACC2/ACACB). In silico screening revealed sesamin (SE) as best-identified hit that showed stable consistent binding all selected LMR. The stability these complexes was validated by a 100 ns simulation run, free calculation determined MM-PBSA method. Interestingly, SE modulated mRNA expression genes involved cell lines, MCF-7 MDA-MB-231, thereby suggesting its an inhibitor

Language: Английский

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Mechanisms and Applications of Apolipoproteins and Apolipoprotein Mimetic Peptides: Common Pathways in Cardiovascular Disease and Cancer

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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The roles, signalling pathways and therapeutic implications of Apoc1 in cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 11, 2025

The apolipoprotein C (Apoc) family comprises a group of low-molecular-weight proteins that are essential for modulating lipoprotein metabolism, primarily influencing lipid transport and metabolic pathways. Apoc1, member the Apoc family, is consistently overexpressed across various cancers, significantly correlating with poor prognosis. multifaceted role Apoc1 includes promoting cancer progression by activating key signalling pathways such as epithelial-mesenchymal transition (EMT), mitogen-activated protein kinases (MAPK), STAT3 WNT3 A. Additionally, contributes to regulatory networks involving lncRNAs miRNAs, thereby cancer. This comprehensive review delineates Apoc1's mechanisms within malignant tumours assesses its prognostic implications patients aim shed light on potential novel therapeutic strategies in oncology, potentially revolutionising patient care enhancing survival rates quality life.

Language: Английский

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The Role of Apolipoproteins in the Commonest Cancers: A Review

Cancers, Journal Year: 2023, Volume and Issue: 15(23), P. 5565 - 5565

Published: Nov. 24, 2023

Apolipoproteins (APOs) are vital structural components of plasma lipoproteins that involved in lipid metabolism and transport. Recent studies have reported an association between apolipoprotein dysregulation the onset a variety human cancers; however, role certain APOs cancer development remains unknown. Based on recent work, we hypothesize might be cancer, with focus most common cancers, including breast, lung, gynecological, colorectal, thyroid, gastric, pancreatic, hepatic, prostate cancers. This review will evidence supporting this hypothesis, mechanisms linking to potential clinical relevance its various inhibitors.

Language: Английский

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