@article{898c6bbba31a4749a8f7515de17de613,
title = "BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma",
abstract = "Background: Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression.Methods: Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice.Results: Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity.Conclusions: BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically.",
keywords = "BAP1, Differentiation, Metastasis, Stem cell, Tumor suppressor, Uveal melanoma",
author = "Matatall, {Katie A.} and Agapova, {Olga A.} and Onken, {Michael D.} and Worley, {Lori A.} and Bowcock, {Anne M.} and Harbour, {J. W.}",
note = "Funding Information: This work was supported by NIH 5R01 CA12597007 (JWH), NIH 1R01 CA16187001 (JWH and AMB), Melanoma Research Alliance (JWH), Melanoma Research Foundation (JWH), The Tumori Foundation (JWH), Research to Prevent Blindness (JWH), Joanna M. Nicolay Melanoma Foundation (KAM), Cancer Biology Pathway of the Division of Biology and Biomedical Sciences at Washington University (KAM), NIH Vision Core Grant P30 EY02687 to the Department of Ophthalmology & Visual Sciences, and an unrestricted grant to the Department of Ophthalmology & Visual Sciences from Research to Prevent Blindness, Inc. We thank Dr. David Razafsky and Dr. Didier Hodzic for their help with the time-lapse microscopy experiments and Belinda McMachan from Ophthalmology Immunomorphology Core Lab, supported by NIH Vision Core Grant P30 EY02687, for mouse tissue processing and staining. We thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Mo., for the use of the Siteman Flow Cytometry Core, which provided cell-sorting services. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant #P30 CA91842. We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1RR024992 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Funding Information: JWH, AMB and Washington University may receive income based on a license of related technology by the University to Castle Biosciences, Inc. This work was not supported by Castle Biosciences, Inc.",
year = "2013",
month = aug,
day = "5",
doi = "10.1186/1471-2407-13-371",
language = "English (US)",
volume = "13",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central",
}