MITF deficiency accelerates GNAQ-driven uveal melanoma
Name
pnas.2107006119.pdf
Description
Published version
Size
2.01 MB
Format
Adobe PDF
Checksum (MD5)
0b8a03b18161b36b08cbf930be52f5b0
Author(s)
Phelps, Grace B
Hagen, Hannah R
Amsterdam, Adam
Lees, Jacqueline A
Date Issued
2022
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Citation
Phelps, Grace B, Hagen, Hannah R, Amsterdam, Adam and Lees, Jacqueline A. 2022. "MITF deficiency accelerates GNAQ-driven uveal melanoma." Proceedings of the National Academy of Sciences of the United States of America, 119 (19).
Version
Final published version
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.
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/PNAS.2107006119
