Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
22
07
2021
accepted:
24
08
2022
pubmed:
14
10
2022
medline:
15
12
2022
entrez:
13
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36229674
doi: 10.1038/s41588-022-01191-z
pii: 10.1038/s41588-022-01191-z
pmc: PMC9729115
doi:
Substances chimiques
IGF1 protein, human
0
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1839-1852Subventions
Organisme : NCI NIH HHS
ID : K99 CA201465
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA163222
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA103846
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
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