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The mechanisms of pro-metastatic role of desmocollin-1 in luminal breast cancer

Název česky Mechanismy prometastatické role desmocollinu-1 v luminálním nádoru prsu
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LAPČÍK Petr ŠULC Petr ČÁPKOVÁ Lenka JANÁČOVÁ Lucia JÍLKOVÁ Kateřina POTĚŠIL David BOUCHALOVÁ Pavla MÜLLER Petr BOUCHAL Pavel

Rok publikování 2019
Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Popis Desmocollin-1 (DSC1) is a protein involved in cell adhesion and tight cell junctions. In our recent study [1] we identified DSC1 as a protein up-regulated in lymph node positive vs. negative primary luminal A breast tumors. Our subsequent objective was to understand the molecular mechanism how DSC1 contributes to lymph node metastasis of luminal A breast cancer and to suggest therapeutically applicable DSC1 modulation. We generated a stably transduced, DSC1 overexpressing cell line originally derived from luminal A breast tumor and named it MCF7-DSC1-GFP. Transwell assay revealed significantly increased migration (p=0.0018) and invasion (p=0.0015) of MCF7-DSC1-GFP cells compared to control MCF7-GFP cells. Based on Gene Set Enrichment Analysis (GSEA) of mRNA microarray data set of 341 luminal A tumors, we selected a panel of potential anti-metastatic inhibitors and found parthenolide as a compound significantly decreasing (p=0.0028) DSC1 protein level in MCF7-DSC1-GFP cells. Flow cytometry revealed increased proportion of MCF7-DSC1-GFP apoptotic cells after parthenolide treatment compared to untreated cells (p=0.006). Quantitative total proteome analysis in data independent acquisition mode on Orbitrap Fusion Lumos mass spectrometer with data analysis in Spectronaut and GSEA showed that DSC1 overexpression in MCF7 cells led to enrichment of pathways involved in cell cycle regulation. It also revealed that parthenolide decreased the levels of DSC1 and cell cycle-associated proteins specifically in MCF7-DSC1-GFP cells. Our work suggests that DSC1 is relevant for breast cancer metastasis via connection with cell migration, invasion and cell cycle regulation and can be modulated by parthenolide, directing breast cancer cells to apoptosis. As such, the data offer novel insights into molecular role of DSC1 in early phase of breast cancer metastasis and possibilities of its modulation in luminal A breast cancer model. References: 1. http://doi.wiley.com/10.1002/pmic.201900073
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