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On the molecular role of desmocollin-­1 in lymph node metastasis of luminal A breast cancer

Název česky Molekulární role desmocollinu-1 při metastázování do lymfatických uzlin u luminálních A nádorů prsu
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LAPČÍK Petr ŠULC Petr ČÁPKOVÁ Lenka JANÁČOVÁ Lucia POTĚŠIL David BOUCHALOVÁ Pavla MÜLLER Petr BOUCHAL Pavel

Druh Konferenční abstrakty
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Popis An increased protein level of desmocollin­1 (DSC1) was found in lymph node positive vs. negative breast cancer in the set of 48 luminal A breast cancer tissues using immunohistochemistry. Generally, DSC1 is involved in desmosomes and cell adhesion and thus may play different roles in different steps of metastatic cascade. The objective of this work was to characterize the molecular role of DSC1 in lymph node metastasis of luminal A breast tumors and delineate possible ways of its potential therapeutic modulation. First, we generated a stably transduced, DSC1 overexpressing cell line derived from the MCF7 line, a model of luminal A breast cancer. Then we selected a panel of potential anti­metastatic inhibitors in luminal A tumors through GSEA analysis of the microarray data set of 341 breast cancer tumors. The effect of the selected inhibitors on DSC1 level was tested in the established cell model, resulting in a significant decrease of DSC1 level in cells exposed to parthenolide (p< 0.010). An increased percentage of apoptotic cells was observed in the cell model after parthenolide treatment using flow cytometry (p< 0.006). Quantitative total proteome analysis confirmed ability of parthenolide to decrease DSC1 levels (q=9.10­4) and pointed out co­regulated proteins (q< 0.05) associated with cell cycle, cell metabolism and tumor progression. An analysis of protein­protein interactions of DSC1 using pulldown assay with directDIA analysis on Orbitrap Fusion Lumos and in Spectronaut software confirmed strong DSC1 interactions with desmoglein­2 (DSG2) and junction plakoglobin (JUP) (q< 1.10­5) and showed novel potential interactors that were associated with cell membrane, desmosomes and cell junctions (q< 0.05). Our work shows 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.
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