25th Annual Meeting of the European Society for Pigment Cell Research, Marseille, France

Metastatic melanoma remains highly lethal despite the efficacy of targeted and immunotherapies. A better understanding of the mechanisms of tumor dissemination is needed to improve treatments. The tumor microenvironment is increasingly recognized as a critical regulator of cancer cell behaviors but the local signals that control melanoma cell spreading remain obscure. The zebrafish is uniquely positioned to probe the multiplicity of external cues influencing cancer cell invasion and dissemination in vivo. We developed genetic engineering tools to rapidly model any melanoma genotype in adult zebrafish, which has allowed us to study the function of candidate cancer genes in tumor initiation and progression. We uncovered a cooperation between the genetic loss of the adherens junction gene, and a drop in the local concentration of the growth factor IGF1 in the regulation of melanoma spread. IGF1 inhibition induced the robust formation of adherens junctions between … we have performed a large-scale genetic screen in zebrafish melanoma to identify cell-surface sensors promoting or hindering melanoma cell dissemination in vivo. These studies delineate new microenvironment-sensing mechanisms governing melanoma spread and suggest potential drug targets to interfere with cancer cell aggressiveness.