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

Cell death & 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

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.

© 2025. The Author(s).

PMID: 41422056

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