Unexpected High Levels of BRN2/POU3F2 Expression in Human Dermal Melanocytic Nevi (Letter)

Abstract

Malignant melanoma is the most aggressive skin cancer. A majority of cancer-associated deaths are due to the invasion of cancer cells to distant tissues. Thus, it is of great importance to understand the mechanisms of metastatic spread. A potential marker for this is BRN2, encoded by the POU3F2 gene, that interacts with SOX transcription factors ( Cook and Sturm, 2008 , Malik et al., 2018 ). While some studies consider BRN2 as a positive regulator of microphthalmia-associated transcription factor (MITF), which favors proliferation ( Goodall et al., 2004a , Wellbrock et al., 2008 ), other studies propose a dual function for BRN2 in both tumor proliferation and invasion, which could be controlled via the upregulation or downregulation of MITF, respectively ( Simmons et al., 2017 , Wellbrock and Arozarena, 2015 ). BRN2 and MITF are present in two distinct sub-populations of cells in 3-dimensional culture ( Thurber et al., 2011 ) and melanoma patient biopsies ( Goodall et al., 2008 , Pinner et al., 2009 ) in which the expression of each transcription factor is mutually exclusive. The relationship between MITF and BRN2 has also been further characterized by showing a role for MITF in the reduction of BRN2 protein levels ( Boyle et al., 2011 ). However, recent single cell gene expression efforts on human primary melanoma cells suggests that the situation may not always be “black and white” with some melanoma cell-expressing genes associated with both high and low levels of BRN2-associated genes in vivo ( Ennen et al., 2017).