Dataset Information

Proteome-Centric Cross-Omics Characterization and Integrated Network Analyses of Triple-Negative Breast Cancer

ABSTRACT: We undertook the first systemic proteomic study of a 90-case cohort of triple-negative breast cancer (TNBC) with a panoramic proteome view in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) were stratified based on the proteome quantification profile and phosphoproteome, each of which exhibited distinct molecular, pathway, and network characteristics. Integrated network analyses of 3 proteomic datasets, together with those of genome and transcriptome from the same cohort, revealed holistic views of altered cellular processes and their regulation by/of upstream/downstream molecules, pathways and functional communities in the background of an integrated molecular network.

ORGANISM(S): Homo Sapiens

SUBMITTER: Weimin Zhu

PROVIDER: PXD028102 | iProX | Tue Aug 24 00:00:00 BST 2021

REPOSITORIES: iProX

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Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

Gong Tian-Qi TQ Jiang Yi-Zhou YZ Shao Chen C Peng Wen-Ting WT Liu Ming-Wei MW Li Da-Qiang DQ Zhang Ben-Yu BY Du Peng P Huang Yin Y Li Fei-Fei FF Li Mu-Yun MY Han Zhao-Lian ZL Jin Xi X Ma Ding D Xiao Yi Y Yang Peng-Yuan PY Qin Jun J Shao Zhi-Ming ZM Zhu Weimin W

Cell reports 20220301 9

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal ...[more]

PMID: 35235781

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Project description:Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and thus inhibiting PI3K/AKT/SREBP/FADS2 axis.

Dataset Information

Proteome-Centric Cross-Omics Characterization and Integrated Network Analyses of Triple-Negative Breast Cancer

Publications

Proteome-centric cross-omics characterization and integrated network analyses of triple-negative breast cancer.

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