The Role of in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin.

Imrich Géci, Peter Bober, Eva Filová, Evžen Amler, Ján Sabo
Author Information
  1. Imrich Géci: Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04011 Košice, Slovakia. ORCID
  2. Peter Bober: Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04011 Košice, Slovakia. ORCID
  3. Eva Filová: Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 142 00 Prague, Czech Republic. ORCID
  4. Evžen Amler: Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 142 00 Prague, Czech Republic.
  5. Ján Sabo: Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04011 Košice, Slovakia.

Abstract

Breast cancer is the most prevalent cancer type in women worldwide. It proliferates rapidly and can metastasize into farther tissues at any stage due to the gradual invasiveness and motility of the tumor cells. These crucial properties are the outcome of the weakened intercellular adhesion, regulated by small guanosine triphosphatases (GTPases), which hydrolyze to the guanosine diphosphate (GDP)-bound conformation. We investigated the inactivating effect of on Rho GTPases involved signaling pathways after treatment with a high dose of doxorubicin. Label-free quantitative proteomic analysis of the proteome isolated from the MCF-7 breast cancer cell line, treated with 1 μM of doxorubicin, identified , , and GTPases that were inactivated by the protein. Upregulation of the GTPases involved in the transforming growth factor-beta (TGF-beta) signaling pathway initiated epithelial-mesenchymal transitions. These findings demonstrate a key role of the protein in the disruption of the cell adhesion and simultaneously allow for a better understanding of the molecular mechanism of the reduced cell adhesion leading to the subsequent metastasis. The conclusions of this study corroborate the hypothesis that chemotherapy with doxorubicin may increase the risk of metastases in drug-resistant breast cancer cells.

Keywords

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Grants

  1. ITMS: 313011AUB1/The Ministry of Education, Science, Research and Sport of the Slovak Republic

MeSH Term

Female
Humans
Breast Neoplasms
cdc42 GTP-Binding Protein
Doxorubicin
GTPase-Activating Proteins
MCF-7 Cells
Proteomics
rac1 GTP-Binding Protein
rho GTP-Binding Proteins
rhoA GTP-Binding Protein

Chemicals

ARHGAP1 protein, human
cdc42 GTP-Binding Protein
Doxorubicin
GTPase-Activating Proteins
rac1 GTP-Binding Protein
rho GTP-Binding Proteins
rhoA GTP-Binding Protein

Word Cloud

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