Dataset Information

Proteomics identification and validation of desmocollin-1 and catechol-O-methyltransferase as proteins associated with breast cancer cell migration and metastasis

ABSTRACT: Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. To identify novel membrane proteins associated with migration and metastasis of breast cancer cells, we selected and characterized a more migrating subpopulation of MDA-MB-231 breast cancer cells. We applied quantitative mass spectrometry with SILAC labeling to analyze their surfaceome and compared it with that of paternal MDA-MB-231 cells. Among 818 identified proteins (FDR < 0.01), 124 differentially abundant cell surface proteins with at least one transmembrane domain were found. Of these, (i) catechol-O-methyltransferase (COMT) was successfully verified as a protein associated with lymph node metastasis of triple negative breast cancer as well as tumor grade by targeted data extraction from the SWATH-MS data set of 96 breast cancer tissues, and (ii) desmocollin-1 (DSC1) was verified as a protein connected with lymph node status of luminal A breast cancer, tumor grade and Her-2 receptor by immunohistochemistry in the same set of patients. Kaplan-Meier analysis associated COMT and DSC1 with decreased overall survival in breast cancer subsets. Our findings indicate importance of both proteins for breast cancer development and metastasis

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Pavel Bouchal

LAB HEAD: Pavel Bouchal

PROVIDER: PXD013162 | Pride | 2019-10-23

REPOSITORIES: Pride

ACCESS DATA

Publications

Proteomics Identification and Validation of Desmocollin-1 and Catechol-O-Methyltransferase as Proteins Associated with Breast Cancer Cell Migration and Metastasis.

Faktor Jakub J Knopfova Lucia L Lapcik Petr P Janacova Lucia L Paralova Vendula V Bouchalova Pavla P Muller Petr P Benes Petr P Bouchal Pavel P

Proteomics 20191028 21-22

Biological treatment of many cancers currently targets membrane bound receptors located on a cell surface. To identify novel membrane proteins associated with migration and metastasis of breast cancer cells, a more migrating subpopulation of MDA-MB-231 breast cancer cell line is selected and characterized. A high-resolution quantitative mass spectrometry with SILAC labeling is applied to analyze their surfaceome and it is compared with that of parental MDA-MB-231 cells. Among 824 identified prot ...[more]

PMID: 31617665

Similar Datasets

Project description:Withaferin A isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to concentrations of Withaferin A (WA) which can be detected systemically in in vivo experiments. Whereas WA revealed attenuation of multiple cancer hallmarks the withanolide analogue Withanone (WN), did not exert any of the described effects in these cells at comparable concentrations. Pathway enrichment analysis identified that WA targeted relevant cancer programs related to cell death, cell cycle and proliferation, which could functionally be validated flow cytometrically and by real-time proliferation xCELLigence assay. With respect to cell motility, invasion and metastasis processes, WA was found to strongly decrease MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This is further supported by gene expression changes which demonstrate increased expression of a validated breast cancer metastasis suppressor gene (BRMS1) and concomitant decreased expression of extracellular matrix-degrading proteases (PLAU, PLAT, ADAM8), cell adhesion molecules (integrins, laminins) as well as pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R). Subsequent in silico network analysis listed key node transcription factors regulating these processes (p53, E2F1, CDKN2A, NRF2) and revealed the role of chromatin modifying enzymes (p300, JARID1B) as central master switches, linking multiple anticancer activities of WA. Furthermore, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking in account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy resistant triple negative breast cancer, WA based therapeutic strategies hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer. Total RNA from 2 different cell lines treated with WA, are compared to their untreated states

Dataset Information

Proteomics identification and validation of desmocollin-1 and catechol-O-methyltransferase as proteins associated with breast cancer cell migration and metastasis

Publications

Proteomics Identification and Validation of Desmocollin-1 and Catechol-O-Methyltransferase as Proteins Associated with Breast Cancer Cell Migration and Metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure