Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4

Diener, Johanna; Baggiolini, Arianna; Pernebrink, Mattias; Dalcher, Damian; Lerra, Luigi; Cheng, Phil F; Varum, Sandra; Häusel, Jessica; Stierli, Salome; Treier, Mathias; Studer, Lorenz; Basler, Konrad; Levesque, Mitchell P; Dummer, Reinhard; Santoro, Raffaella; Cantù, Claudio; Sommer, Lukas

doi:10.1038/s41467-021-25326-8

Citations

Citation copied

Diener, J., Baggiolini, A., Pernebrink, M., Dalcher, D., Lerra, L., Cheng, P. F., Varum, S., Häusel, J., Stierli, S., Treier, M., Studer, L., Basler, K., Levesque, M. P., Dummer, R., Santoro, R., Cantù, C., & Sommer, L. (2021). Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4. Nature Communications, 12(1), 5056. https://doi.org/10.1038/s41467-021-25326-8

Abstract

Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::Nras$^{Q61K}$; Cdkn2a$^{−/−}$ melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a