Ablain J, Al Mahi A, Rothschild H, Prasad M, Aires S, Yang S, Dokukin ME, Xu S, Dang M, Sokolov I, Lian CG, Zon LI. 2022. Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion. Nature genetics. 54(12):1839-1852. Pubmed: 36229674 DOI:10.1038/s41588-022-01191-z


Cancer genetics has uncovered many tumor-suppressor and oncogenic pathways, but few alterations have revealed mechanisms involved in tumor spreading. Here, we examined the role of the third most significant chromosomal deletion in human melanoma that inactivates the adherens junction gene NECTIN1 in 55% of cases. We found that NECTIN1 loss stimulates melanoma cell migration in vitro and spreading in vivo in both zebrafish and human tumors specifically in response to decreased IGF1 signaling. In human melanoma biopsy specimens, adherens junctions were seen exclusively in areas with low IGF1 levels, but not in NECTIN1-deficient tumors. Our study establishes NECTIN1 as a major determinant of melanoma dissemination and uncovers a genetic control of the response to microenvironmental signals.
© 2022. The Author(s).

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The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.

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