The major oncogenes that drive melanoma are well known, and researchers have also characterized many of the mutations that affect the activity of tumor suppressors like PTEN in the cancer. But less is known about how the levels of tumor suppressor affect total tumor suppressor activity in this cancer. A study led by Ludwig Oxford’s Colin Goding and Lionel Larue of the Institut Curie, in France, identified BRN2 as a noncanonical tumor suppressor that regulates PTEN levels whose partial insufficiency can drive melanoma. The authors showed previously that BRN2 is a key transcription factor that lies downstream of three melanoma-associated signaling pathways to control gene expression, and that in vitro and in xenograft experiments BRN2 controls melanoma migration and invasiveness. The researchers reported in Nature Communications in June using mice in which BRN2 is specifically inactivated in mouse melanocytes that loss of BRN2 increases melanoma initiation, and that low levels of BRN2 promote metastatic dissemination. This is the first time that the function of BRN2 in melanoma initiation and metastasis has been demonstrated in an animal model engineered to develop melanoma. The authors also reported that BRN2 loss or low levels are linked to worse prognoses in melanoma.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).