PUBLICATION
MITF deficiency accelerates GNAQ-driven uveal melanoma
- Authors
- Phelps, G.B., Hagen, H.R., Amsterdam, A., Lees, J.A.
- ID
- ZDB-PUB-220506-22
- Date
- 2022
- Source
- Proceedings of the National Academy of Sciences of the United States of America 119: e2107006119 (Journal)
- Registered Authors
- Amsterdam, Adam
- Keywords
- melanoma, mitf, uveal, zebrafish
- MeSH Terms
-
- GTP-Binding Protein alpha Subunits, Gq-G11/genetics
- Humans
- Melanoma*/pathology
- Microphthalmia-Associated Transcription Factor/genetics
- Skin Neoplasms*
- Uveal Neoplasms*/genetics
- Uveal Neoplasms*/pathology
- Uveal Neoplasms*/therapy
- PubMed
- 35512098 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Phelps, G.B., Hagen, H.R., Amsterdam, A., Lees, J.A. (2022) MITF deficiency accelerates GNAQ-driven uveal melanoma. Proceedings of the National Academy of Sciences of the United States of America. 119:e2107006119.
Abstract
Significance Uveal melanoma (UM) is a cancer of eye melanocytes. Although relatively rare, UM is extremely deadly, as approximately half of all patients develop liver metastases for which there are no approved therapies. Even therapies that succeed in cutaneous melanoma (CM) treatment have proven ineffectual for UM, highlighting both the distinct nature of these two melanomas and the need to understand the differences between them. Here, we show that autochthonous UM tumors are rapidly induced by activated YAP and can lack hyperactive ERK, highlighting YAP as a promising therapeutic target. We further show that MITF functions as a tumor suppressor in UM in contrast to its essential role in CM, establishing that MITF inhibition should not be entertained for UM treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping