Page 90 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

are needed, these findings support the potential role of alkalization strategies in oncology.

Acknowledgments and funding: The work was funded by a grant from the Russian Science Foundation № 24-15-
00297, https://rscf.ru/en/project/24-15-00297/, and was supported by the Health Committee of Saint Petersburg state
assignment for N.P. Napalkov Saint Petersburg Clinical Research and Practical Center of Specialized Types of Medical
Care (Oncological).

L31
Interplay between redox regulation and cancer metabolism

Monika Minarić , Ivan Lučić , Lidija Milković , Ana Čipak Gašparović 1
1
1
1
1Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia
Keywords: cancer, metabolism, antioxidant, NRF2, aquaporin

Background: Redox regulation is vital for maintaining normal cellular function. Key to this regulation is the control
of the flux of hydrogen peroxide (H₂O₂), which can be a key event, as H₂O₂ functions as a signaling molecule at low
concentrations but is cytotoxic at high levels. Pores that mediate H₂O₂ permeability across membranes are therefore
critical in maintaining redox homeostasis. Therefore, aquaporins (AQPs), initially defined as water channels, have
emerged as important players. Aquaglyceroporins, a group of aquaporins, facilitate not only water but also small
solute transport, including H₂O₂ and glycerol. By modulating H₂O₂ permeability, AQPs can influence redox-sensitive
signalling pathways involved in tumor development and progression. Moreover, by facilitating glycerol transport, AQPs
can regulate metabolic pathways, suggesting an important role in cancer cell physiology.
Materials and Methods: This study focuses on aquaglyceroporin AQP3 in breast cancer cell lines. Our primary objective
was to investigate the role of AQP3 in mediating glycerol flux across the plasma membrane and its impact on cellular
metabolism. We also assessed how glucose levels influence AQP expression. Furthermore, we explored whether NRF2,
the master regulator of antioxidant responses, can modulate the expression of AQP3 and AQP5.
Results: Our results demonstrate that glucose levels influence the expression of AQP as well as NRF2. Also, modulation
of NRF2 influences the levels of AQP3.
Conclusions: Our results suggest a potential regulation between NRF2 and AQPs, suggesting that redox and metabolic
pathways are closely linked via these membrane channels. The observed glucose-dependent modulation of both AQPs
and NRF2 indicates possible crosstalk that could contribute to the metabolic flexibility and stress resistance of cancer
cells.

Acknowledgments and funding: This research was funded by the HRZZ-IP-2020-02-3617 grant.

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