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

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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.
Funding Information
  • Deutsche Forschungsgemeinschaft (IRTG2168 No. 272482170)
  • Deutsche Forschungsgemeinschaft (TRR237 No. 369799452)
  • Deutsche Forschungsgemeinschaft (TRR259 No. 397484323)
  • Deutsche Forschungsgemeinschaft (SFB1454 No. 432325352)
  • Deutsche Forschungsgemeinschaft (EXC2151 No. 390873048)

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