Abstract A13: MSX1-induced neural crest-like reprograming promotes melanoma progression

Abstract

Abstract Melanoma cells share many biological properties with neural crest cells. Here, we show that the homeodomain transcription factor Msh homeobox 1 (MSX1), which is essential for neural crest specification, reprograms melanocytes towards a neural crest precursor-like state. MSX1-reprogrammed melanocytes express the neural crest marker p75 and are able to differentiate into neuronal and mesenchymal lineages. Mechanistically, MSX1 suppresses the proximal promoter of microphthalmia-associated transcription factor (MITF), the master transcriptional regulator of melanogenesis. MSX1 expression is also significantly correlated with melanoma progression. MSX1 prompts melanoma cell motility and depletion of MSX1 significantly inhibits melanoma metastasis. These results demonstrate that not only can neural crest-like reprogramming in melanocytes be achieved by a single factor, but also that similar dedifferentiation is a critical process for melanoma progression. Citation Format: Markus V. Heppt, Wang X. Joshua, Denitsa M. Hristova, Zhi Wei, Martin Irmler, Carola Berking, Robert Besch, Johannes Beckers, Frank J. Rauscher, III, David E. Fisher, Meenhard Herlyn, Mizuho Fukunaga-Kalabis. MSX1-induced neural crest-like reprograming promotes melanoma progression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A13.