Tumor-induced metabolic immunosuppression: Mechanisms and therapeutic targets

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115206 - 115206

Published: Jan. 1, 2025

Language: Английский

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Oncometabolite D-2HG drives tumor metastasis and protumoral macrophage polarization by targeting FTO/m6A/ANGPTL4/integrin axis in triple-negative breast cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Feb. 6, 2025

Abstract Background D-2-hydroxyglutarate (D-2HG), an oncometabolite derived from the tricarboxylic acid cycle. Previous studies have reported diverse effects of D-2HG in pathophysiological processes, yet its role breast cancer remains largely unexplored. Methods We applied advanced biosensor approach to detect levels samples. then investigated biological functions through multiple vitro and vivo assays. A joint MeRIP-seq RNA-seq strategy was used identify target genes regulated by D-2HG-mediated N6-methyladenosine (m 6 A) modification. RNA pull-down assays were further reader that could specifically recognize m modification on angiopoietin like 4 (ANGPTL4) mRNA immunoprecipitation confirm findings. Results found accumulated triple-negative (TNBC), exerting oncogenic both promoting TNBC cell growth metastasis. Mechanistically, enhanced global modifications cells, notably upregulating ANGPTL4 mRNA, which mediated inhibition Fat-mass obesity-associated protein (FTO), resulting increased recognition A-modified YTH binding F1 (YTHDF1), thereby translation ANGPTL4. As a secretory protein, subsequently activated integrin-mediated JAK2/STAT3 signaling cascade cells autocrine signaling. Notably, knockdown or treatment with GLPG1087 (an integrin antagonist) significantly reduced D-2HG-induced proliferation metastasis cells. Additionally, promote macrophage M2 polarization within tumor microenvironment via paracrine signaling, driving progression. The association poor prognosis patients underscores clinical relevance. Conclusions Our study unveils previously unrecognized for progression targeting D-2HG/FTO/m A/ANGPTL4/integrin axis can serve as promising therapeutic patients.

Language: Английский

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Single extracellular vesicle analysis for early cancer detection

Trends in Molecular Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 681 - 692

Published: May 24, 2022

Language: Английский

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Integrative Serum Metabolic Fingerprints Based Multi‐Modal Platforms for Lung Adenocarcinoma Early Detection and Pulmonary Nodule Classification

Advanced Science, Journal Year: 2022, Volume and Issue: 9(34)

Published: Oct. 18, 2022

Identification of novel non-invasive biomarkers is critical for the early diagnosis lung adenocarcinoma (LUAD), especially accurate classification pulmonary nodule. Here, a multiplexed assay developed on an optimized nanoparticle-based laser desorption/ionization mass spectrometry platform sensitive and selective detection serum metabolic fingerprints (SMFs). Integrative SMFs based multi-modal platforms are constructed LUAD The dual modal model, with protein tumor marker neural network (MP-NN), integrating carcinoembryonic antigen (CEA) via deep learning, shows superior performance compared single model Met-NN (p < 0.001). Based MP-NN, tri MPI-RF SMFs, CEA, image features random forest demonstrates significantly higher than clinical models (Mayo Clinic Veterans Affairs) artificial intelligence in nodule would be promising tools screening management, paving conceptual practical foundation application omics tools.

Language: Английский

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Untargeted metabolomics by liquid chromatography‐mass spectrometry for food authentication: A review

Comprehensive Reviews in Food Science and Food Safety, Journal Year: 2022, Volume and Issue: 21(3), P. 2455 - 2488

Published: March 29, 2022

Abstract Food fraud is currently a growing global concern with far‐reaching consequences. authenticity attributes, including biological identity, geographical origin, agricultural production, and processing technology, are susceptible to food fraud. Metabolic markers their corresponding authentication methods considered as promising choice for authentication. However, few metabolic were available develop robust analytical in routine control. Untargeted metabolomics by liquid chromatography‐mass spectrometry (LC‐MS) increasingly used discover markers. This review summarizes the general workflow, recent applications, advantages, advances, limitations, future needs of untargeted LC‐MS identifying In conclusion, shows great efficiency assessment freshness, cause animals’ death, so on, through three main steps, namely, data acquisition, biomarker discovery, validation. The application prospects selected require be valued, need eventually applicable at targeted analysis assessing unknown samples.

Language: Английский

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