High-salt diet induces immune-independent re-differentiation, metabolic shut down and cell cycle arrest of melanoma

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.

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Publication Details

Journal
Cell Death and Disease
Published
2025-12-20
DOI
https://doi.org/10.1038/s41419-025-08329-x
Primary Topic
Sodium Intake and Health
Type
article
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article

High-salt diet induces immune-independent re-differentiation, metabolic shut down and cell cycle arrest of melanoma

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Sodium Intake and Health
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High-salt diet induces immune-independent re-differentiation, metabolic shut down and cell cycle arrest of melanoma

Ann‐Kathrin Baumgart, Patrick Neubert, Michael Hölzel, Christian Münch, Jelena Zurkovic, Melanie Eichler, Christoph Heuser, Clivia Lisowski, Christoph Wilhelm, Marcel Michla, Olena Babyak, Thomas Becker, Agnes Schröder, Matthias Eckhardt, Natascha E. Stumpf, Christian Kurts, Annkristin Heine, Lea Seep, Jonathan Jantsch, Jana Liebing, Katarzyna Jobin, Daniel Hinze, Janine Becker-Gotot, Süleyman Bozkurt, Mirjam Meißner, Christoph Thiele, Vanessa Schmitt, Daniela Klaus
article en

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.

Cell Death and DiseaseVol. 17(1)
Goethe University Frankfurt (DE), University of Bonn (DE), Baker Heart and Diabetes Institute (AU), University of Cologne (DE), University of Würzburg (DE), University Hospital Bonn (DE), University Hospital Regensburg (DE), University Hospital Cologne (DE), Life & Brain (Germany) (DE), University of Regensburg (DE)
Openalex Percentile: Top 52%
Sodium Intake and Health
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