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

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 phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4

SUBMITTER: Diener J 

PROVIDER: S-EPMC8379183 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature