High-salt diet induces immune-independent re-differentiation, metabolic shut down and cell cycle arrest of melanoma
Year: 2025
Type: article
Abstract: High salt diet (HSD) is known to reduce cancer growth in some tumor models, which has been attributed to tissue accumulation of sodium that enhances local anti-tumor immunity. Here, we show that a HSD inhibits melanoma growth independent of sodium accumulation and immune cells in skin and lung. Melanoma cells from mice on a HSD upregulated the metabolic inhibitor Tuberous sclerosis complex 2 (TSC2), causing metabolic shutdown despite nutrient availability. Furthermore, Microphthalmia-associated transcription factor (MITF), a crucial regulator of melanoma metabolism and differentiation, was upregulated, resulting in enhanced melanogenesis and cell cycle arrest. Thus, a HSD reversed the de-differentiation of melanoma cells and promoted their re-differentiation into a "normal" melanocytic state. These findings suggest that the anti-tumor effect of HSD may be tumor-specific and in some cases immune cell-independent.
Source: Cell Death and Disease
Authors: Clivia Lisowski, Natascha E. Stumpf, Katarzyna Jobin, Daniela Klaus, Melanie Eichler, Ann-Kathrin Baumgart, Olena Babyak, Mirjam Meißner, Agnes Schröder, Patrick Neubert, Vanessa Schmitt, Marcel Michla, Süleyman Bozkurt, Jelena Zurkovic, Daniel Hinze, Jana Liebing, Matthias Eckhardt, Christoph Heuser, Lea Seep, Annkristin Heine, Janine Becker-Gotot, Christoph Thiele, Christian Münch, Thomas Becker, Jonathan Jantsch, Christoph Wilhelm, Michael Hölzel, Christian Kurts
Institutions: University of Bonn, University Hospital Bonn, University of Würzburg, University Hospital Regensburg, Institute of Medical Microbiology and Hygiene, University of Regensburg, Baker Heart and Diabetes Institute, Goethe University Frankfurt, Leibniz Institute for Immunotherapy, University of Cologne, University Hospital Cologne
Language: English
Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
Funder: Deutsche Forschungsgemeinschaft
OpenAlex ID: W4417523666