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

a 2019

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

LAPČÍK, Petr, Petr ŠULC, Lenka ČÁPKOVÁ, Lucia JANÁČOVÁ, Kateřina JÍLKOVÁ et. al.

Základní údaje

Originální název

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

Název česky

Mechanismy prometastatické role desmocollinu-1 v luminálním nádoru prsu

Autoři

LAPČÍK, Petr, Petr ŠULC, Lenka ČÁPKOVÁ, Lucia JANÁČOVÁ, Kateřina JÍLKOVÁ, David POTĚŠIL, Pavla BOUCHALOVÁ, Petr MÜLLER a Pavel BOUCHAL

Vydání

XX. setkání biochemiků a molekulárních biologů, 12.-13.11.2019, in Book of Abstracts, p. 38. 2019

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Přírodovědecká fakulta

Změněno: 24. 1. 2020 10:40, doc. Mgr. Pavel Bouchal, Ph.D.

Anotace

V originále

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

Návaznosti

GA17-05957S, projekt VaV

Název: Evaluace nových potenciálních cílů a inhibitorů pro blokování vývoje metastáz u luminálních A nádorů prsu

Investor: Grantová agentura ČR, Evaluace nových potenciálních cílů a inhibitorů pro blokování vývoje metastáz u luminálních A nádorů prsu

MUNI/A/1575/2018, interní kód MU

Název: Podpora biochemického výzkumu v roce 2019

Investor: Masarykova univerzita, Podpora biochemického výzkumu v roce 2019, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

LAPČÍK, Petr, Petr ŠULC, Lenka ČÁPKOVÁ, Lucia JANÁČOVÁ, Kateřina JÍLKOVÁ, David POTĚŠIL, Pavla BOUCHALOVÁ, Petr MÜLLER a Pavel BOUCHAL. The mechanisms of pro-metastatic role of desmocollin-1 in luminal breast cancer. In XX. setkání biochemiků a molekulárních biologů, 12.-13.11.2019, in Book of Abstracts, p. 38. 2019.

@proceedings{1587097,
   author = {Lapčík, Petr and Šulc, Petr and Čápková, Lenka and Janáčová, Lucia and Jílková, Kateřina and Potěšil, David and Bouchalová, Pavla and Müller, Petr and Bouchal, Pavel},
   booktitle = {XX. setkání biochemiků a molekulárních biologů, 12.-13.11.2019, in Book of Abstracts, p. 38.},
   language = {eng},
   title = {The mechanisms of pro-metastatic role of desmocollin-1 in luminal breast cancer},
   year = {2019}
}

TY  - CONF
ID  - 1587097
AU  - Lapčík, Petr - Šulc, Petr - Čápková, Lenka - Janáčová, Lucia - Jílková, Kateřina - Potěšil, David - Bouchalová, Pavla - Müller, Petr - Bouchal, Pavel
PY  - 2019
TI  - The mechanisms of pro-metastatic role of desmocollin-1 in luminal breast cancer
N2  - 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
ER  -

LAPČÍK, Petr, Petr ŠULC, Lenka ČÁPKOVÁ, Lucia JANÁČOVÁ, Kateřina JÍLKOVÁ, David POTĚŠIL, Pavla BOUCHALOVÁ, Petr MÜLLER a Pavel BOUCHAL. The mechanisms of pro-metastatic role of desmocollin-1 in luminal breast cancer. In \textit{XX. setkání biochemiků a molekulárních biologů, 12.-13.11.2019, in Book of Abstracts, p. 38.}. 2019.

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