STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway.

ABSTRACT: Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association with melanocyte inducing transcription factor (MITF) expression levels. We established a mouse melanoma model for deleting Stat3 in melanocytes with specific expression of human hyperactive NRAS^Q61K in an Ink4a-deficient background, two frequent driver mutations in human melanoma. Mice devoid of Stat3 showed early disease onset with higher proliferation in primary tumors, but displayed significantly diminished lung, brain, and liver metastases. Whole-genome expression profiling of tumor-derived cells also showed a reduced inva

SUBMITTER: Swoboda A 

PROVIDER: S-EPMC7116782 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature