Aquaporin water channels affect the response of conventional anticancer therapies of 3D grown breast cancer cells

Edamana, Sarannya; Pedersen, Stine Falsig; Nejsum, Lene N.

doi:10.1016/j.bbrc.2022.11.096

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…The fact that other peroxiporins may also be contributing to the regulation of this pathway, as in glioma and colon cancer cells where AQP5 affects the EGFR/PI3K/Akt signaling pathway [35,36], cannot be disregarded. Considering that AQP3 silencing in MCF7 cells caused decreased sensitivity to nucleotide analogs 5-FU and gemcitabine [37], while its overexpression in MCF7 spheroids decreased viability in response to cisplatin, 5-FU, and doxorubicin [38], there is a great need to investigate pathways modulated by peroxiporin(s).…”

Section: Discussionmentioning

confidence: 99%

AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells

Mlinarić

Lučić

Milković

et al. 2023

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells

Mlinarić

Lučić

Milković

et al. 2023

IJMS

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“…Of note, we recently found that AQP1, AQP3 and AQP5 differentially affected the response of 3D-grown human breast cancer spheroids to conventional anticancer therapies [55]. AQP3 overexpression reduced cell viability in response to Cisplatin, 5-Fluorouracil (5-FU) and Doxorubicin, as well as a combination of the three treatments.…”

Section: Discussionmentioning

confidence: 99%

Aquaglyceroporins in Human Breast Cancer

Kirkegaard,

Riishede,

Tramm

et al. 2023

Cells

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Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.

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“…The silencing of AQP5 in this resistant strain resulted in decreased proliferation and induction of apoptosis [ 131 ]. Yet, in the AQP5-overexpressing MDA-MB-231 spheroids doxorubicin, a combination of doxorubicin, cisplatin, and 5-FU or a combination with the Ras inhibitor salirasib, but not cisplatin and 5-FU alone, reduced the spheroid size and viability, indicating the role of AQP5 in the sensitivity to doxorubicin [ 132 ]. Furthermore, AQP5 with a mutation for the Ras binding site S156A did not affect the spheroid size, suggesting that Ras could have a role in the increased sensitivity to doxorubicin [ 132 ].…”

Section: Peroxiporins As Potential Targets In Tnbc Therapymentioning

confidence: 99%

Peroxiporins in Triple-Negative Breast Cancer: Biomarker Potential and Therapeutic Perspectives

Bijelić,

Silovski,

Mlinarić

et al. 2024

IJMS

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Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes since it is initially characterized by the absence of specific biomarkers and corresponding targeted therapies. Advances in methodology, translational informatics, genomics, and proteomics have significantly contributed to the identification of therapeutic targets. The development of innovative treatments, such as antibody–drug conjugates and immune checkpoint inhibitors, alongside chemotherapy, has now become the standard of care. However, the quest for biomarkers defining therapy outcomes is still ongoing. Peroxiporins, which comprise a subgroup of aquaporins, which are membrane pores facilitating the transport of water, glycerol, and hydrogen peroxide, have emerged as potential biomarkers for therapy response. Research on peroxiporins reveals their involvement beyond traditional channeling activities, which is also reflected in their cellular localization and roles in cellular signaling pathways. This research on peroxiporins provides fresh insights into the mechanisms of therapy resistance in tumors, offering potential avenues for predicting treatment outcomes and tailoring successful TNBC therapies.

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Aquaporin water channels affect the response of conventional anticancer therapies of 3D grown breast cancer cells

Cited by 9 publications

References 46 publications

AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells

AQP3-Dependent PI3K/Akt Modulation in Breast Cancer Cells

Aquaglyceroporins in Human Breast Cancer

Peroxiporins in Triple-Negative Breast Cancer: Biomarker Potential and Therapeutic Perspectives

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