PUBLICATION
Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion
- Authors
- Ablain, J., Al Mahi, A., Rothschild, H., Prasad, M., Aires, S., Yang, S., Dokukin, M.E., Xu, S., Dang, M., Sokolov, I., Lian, C.G., Zon, L.I.
- ID
- ZDB-PUB-221018-52
- Date
- 2022
- Source
- Nature Genetics 54(12): 1839-1852 (Journal)
- Registered Authors
- Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Animals
- Humans
- Insulin-Like Growth Factor I/genetics
- Melanoma*/genetics
- Zebrafish*/genetics
- PubMed
- 36229674 Full text @ Nat. Genet.
Citation
Ablain, J., Al Mahi, A., Rothschild, H., Prasad, M., Aires, S., Yang, S., Dokukin, M.E., Xu, S., Dang, M., Sokolov, I., Lian, C.G., Zon, L.I. (2022) Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion. Nature Genetics. 54(12):1839-1852.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping