Dataset Information

Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.

ABSTRACT: Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, whereas the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375, and RKO cells treated for 48 h with 5-fluorouracil, methotrexate and paclitaxel. Individually, the proteomic data on attached and detached cells had comparable performance in target and drug mechanism deconvolution, whereas the combined data significantly improved the target ranking for paclitaxel. Comparative analysis of attached versus detached proteomes provided further insight into cell life and death decision making. Six proteins consistently up- or downregulated in the detached versus attached cells regardless of the drug and cell type were discovered; their role in cell death/survival was tested by silencing them with siRNA. Knocking down USP11, CTTN, ACAA2, and EIF4H had anti-proliferative effects, affecting UHRF1 additionally sensitized the cells to the anticancer drugs, while knocking down RNF-40 increased cell survival against the treatments. Therefore, adding detached cells to the expression proteomics analysis of drug-treated cells can significantly increase the analytical value of the approach. The data have been deposited to the ProteomeXchange with identifier PXD007686.

SUBMITTER: Saei AA

PROVIDER: S-EPMC5986252 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.

Saei Amir Ata AA Sabatier Pierre P Tokat Ülkü Güler ÜG Chernobrovkin Alexey A Pirmoradian Mohammad M Zubarev Roman A RA

Molecular & cellular proteomics : MCP 20180323 6

Chemotherapeutics cause the detachment and death of adherent cancer cells. When studying the proteome changes to determine the protein target and mechanism of action of anticancer drugs, the still-attached cells are normally used, whereas the detached cells are usually ignored. To test the hypothesis that proteomes of detached cells contain valuable information, we separately analyzed the proteomes of detached and attached HCT-116, A375, and RKO cells treated for 48 h with 5-fluorouracil, methot ...[more]

PMID: 29572246

Similar Datasets

Project description:Carotenoids are colorful lipophilic isoprenoids synthesized in all photosynthetic organisms which play roles in plant growth and development and provide numerous health benefits in the human diet (precursor of Vitamin A). The commercially popular kiwifruits are golden yellow-fleshed (Actinidia chinensis) and green fleshed (A. deliciosa) cultivars which have a high carotenoid concentration. Understanding the molecular mechanisms controlling the synthesis and sequestration of carotenoids in Actinidia species is key to increasing nutritional value of this crop via breeding. In this study we analyzed fruit with varying flesh color from three Actinidia species; orange-fleshed A. valvata (OF), yellow-fleshed A. polygama (YF) and green-fleshed A. arguta (GF). Microscopic analysis revealed that carotenoids accumulated in a crystalline form in YF and OF chromoplasts, with the size of crystals being bigger in OF compared to YF, which also contained globular substructures in the chromoplast. Metabolic profiles were investigated using ultra-performance liquid chromatography (UPLC), which showed that β-carotene was the predominant carotenoid in the OF and YF species, while lutein was the dominant carotenoid in the GF species. Global changes in gene expression were studied between OF and GF (both tetraploid) species using RNA-sequencing which showed higher expression levels of upstream carotenoid biosynthesis-related genes such as DXS, PSY, GGPPS, PDS, ZISO, and ZDS in OF species compared to GF. However, low expression of downstream pathway genes was observed in both species. Pathway regulatory genes (OR and OR-L), plastid morphology related genes (FIBRILLIN), chlorophyll degradation genes (SGR, SGR-L, RCCR, and NYC1) were upregulated in OF species compared to GF. This suggests chlorophyll degradation (primarily in the initial ripening stages) is accompanied by increased carotenoid production and localization in orange flesh tissue, a contrast from green flesh tissue. These results suggest a coordinated change in the carotenoid pathway, as well as changes in plastid type, are responsible for an orange phenotype in certain kiwifruit species.

Dataset Information

Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.

Publications

Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets