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AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells

Mlinarić, Monika; Lučić, Ivan; Milković, Lidija; da Silva, Inês V.; Tartaro Bujak, Ivana; Musani, Vesna; Soveral, Graça; Čipak Gašparović, Ana (2023) AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells. International journal of molecular sciences, 24 (9). ISSN 1422-0067

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Aquaporin 3 (AQP3) is a peroxiporin, a membrane protein that channels hydrogen peroxide in addition to water and glycerol. AQP3 expression also correlates with tumor progression and malignancy and is, therefore, a potential target in breast cancer therapy. In addition, epithelial growth factor receptor (EGFR) plays an important role in breast cancer. Therefore, we investigated whether disruption of the lipid raft harboring EGFR could affect AQP3 expression, and conversely, whether AQP3 silencing would affect the EGFR/phosphoinositide-3- kinase (PI3K)/Protein kinase B (PKB or Akt) signaling pathway in breast cancer cell lines with different malignant capacities. We evaluated H2O2 uptake, cell migratory capacity, and expression of PI3K, pAkt/Akt in three breast cancer cell lines, MCF7, SkBr3, and SUM159PT, and in the nontumorigenic breast epithelial cell line MCF10A. Our results show different responses between the tested cell lines, especially when compared to the nontumorigenic cell line. Neither lipid raft disruption nor EGF stimuli had an effect on PI3K/Akt pathway in MCF10A cell line. AQP3-silencing in SkBr3 and SUM159PT showed that AQP3 can modulate PI3K/Akt activation in these cells. Interestingly, SUM159PT cells increase nuclear factor-E2–related factor 2 (NRF2) in response to lipid raft disruption and EGF stimuli, suggesting an oxidative-dependent response to these treatments. These results suggest that in breast cancer cell lines, AQP3 is not directly related to PI3K/Akt pathway but rather in a cell-line-dependent manner.

Item Type: Article
Uncontrolled Keywords: AQP3 ; PI3K/Akt ; NRF2
Subjects: NATURAL SCIENCES > Biology
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Određivanje uloga akvaporina 3 i 5 u razvoju rezistencije tumora dojke na oksidacijski stresČipak Gašparović, AnaIP-2020-02-3617HRZZ
Depositing User: Ana Čipak Gašparović
Date Deposited: 16 Jun 2023 08:12
DOI: 10.3390/ijms24098133

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