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

• Published in: International journal of molecular sciences Vol. 24; no. 14; p. 11352
• Main Authors: Géci, Imrich, Bober, Peter, Filová, Eva, Amler, Evžen, Sabo, Ján
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.07.2023; MDPI
• Subjects: Breast cancer; Cancer therapies; cell adhesion; Cell adhesion & migration; doxorubicin; Drug dosages; Drug resistance; Ions; Mass spectrometry; metastases; Metastasis; Morphology; Motility; Proteins; proteomics; Scientific imaging; Signal transduction; Stem cells; metastases; breast cancer; mass spectrometry; doxorubicin; proteomics; cell adhesion
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241411352

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.