KIT Suppresses BRAF^V600E-Mutant Melanoma by Attenuating Oncogenic RAS/MAPK Signaling.

ABSTRACT: The receptor tyrosine kinase KIT promotes survival and migration of melanocytes during development, and excessive KIT activity hyperactivates the RAS/MAPK pathway and can drive formation of melanomas, most notably of rare melanomas that occur on volar and mucosal surfaces of the skin. The much larger fraction of melanomas that occur on sun-exposed skin is driven primarily by BRAF- or NRAS-activating mutations, but these melanomas exhibit a surprising loss of KIT expression, which raises the question of whether loss of KIT in these tumors facilitates tumorigenesis. To address this question, we introduced a kit(lf) mutation into a strain of Tg(mitfa:BRAF^V600E); p53(lf) melanoma-prone zebrafish. Melanoma onset was accelerated in kit(lf); Tg(mitfa:BRAF^V600E

SUBMITTER: Neiswender JV 

PROVIDER: S-EPMC5679278 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature