BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma

Katie A. Matatall, Olga A. Agapova, Michael D. Onken, Lori A. Worley, Anne M. Bowcock, J. William Harbour

Research output: Contribution to journalArticle

57 Citations (Scopus)

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.

Original languageEnglish
Article number371
JournalBMC Cancer
Volume13
DOIs
StatePublished - Aug 5 2013

Fingerprint

Stem Cells
Neoplasm Metastasis
SCID Mice
Melanocytes
Bromodeoxyuridine
RNA Interference
Transcriptome
Cell Differentiation
Neoplasms
Flow Cytometry
Uveal melanoma
Mutation

Keywords

  • BAP1
  • Differentiation
  • Metastasis
  • Stem cell
  • Tumor suppressor
  • Uveal melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Matatall, K. A., Agapova, O. A., Onken, M. D., Worley, L. A., Bowcock, A. M., & William Harbour, J. (2013). BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma. BMC Cancer, 13, [371]. https://doi.org/10.1186/1471-2407-13-371

BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma. / Matatall, Katie A.; Agapova, Olga A.; Onken, Michael D.; Worley, Lori A.; Bowcock, Anne M.; William Harbour, J.

In: BMC Cancer, Vol. 13, 371, 05.08.2013.

Research output: Contribution to journalArticle

Matatall, Katie A. ; Agapova, Olga A. ; Onken, Michael D. ; Worley, Lori A. ; Bowcock, Anne M. ; William Harbour, J. / BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma. In: BMC Cancer. 2013 ; Vol. 13.
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