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Article

The Role of ARHGAP1 in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin

1
Department of Medical and Clinical Biophysics, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04011 Košice, Slovakia
2
Institute of Experimental Medicine, Czech Academy of Sciences, Vídeňská 1083, 142 00 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(14), 11352; https://doi.org/10.3390/ijms241411352
Submission received: 3 June 2023 / Revised: 5 July 2023 / Accepted: 8 July 2023 / Published: 12 July 2023
(This article belongs to the Special Issue Molecular Biology of Breast Cancer)

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 ARHGAP1 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 RAC1, CDC42, and RHOA GTPases that were inactivated by the ARHGAP1 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 ARHGAP1 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: proteomics; mass spectrometry; cell adhesion; breast cancer; doxorubicin; metastases proteomics; mass spectrometry; cell adhesion; breast cancer; doxorubicin; metastases
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MDPI and ACS Style

Géci, I.; Bober, P.; Filová, E.; Amler, E.; Sabo, J. The Role of ARHGAP1 in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin. Int. J. Mol. Sci. 2023, 24, 11352. https://doi.org/10.3390/ijms241411352

AMA Style

Géci I, Bober P, Filová E, Amler E, Sabo J. The Role of ARHGAP1 in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin. International Journal of Molecular Sciences. 2023; 24(14):11352. https://doi.org/10.3390/ijms241411352

Chicago/Turabian Style

Géci, Imrich, Peter Bober, Eva Filová, Evžen Amler, and Ján Sabo. 2023. "The Role of ARHGAP1 in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin" International Journal of Molecular Sciences 24, no. 14: 11352. https://doi.org/10.3390/ijms241411352

APA Style

Géci, I., Bober, P., Filová, E., Amler, E., & Sabo, J. (2023). The Role of ARHGAP1 in Rho GTPase Inactivation during Metastasizing of Breast Cancer Cell Line MCF-7 after Treatment with Doxorubicin. International Journal of Molecular Sciences, 24(14), 11352. https://doi.org/10.3390/ijms241411352

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