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BAP1 Plays a Survival Role in Cutaneous Melanoma.

Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, JennyC-N; Jönsson, Göran B LU ; Tompers Frederick, Dennie and Tsao, Hensin (2015) In Journal of Investigative Dermatology 135(4). p.1089-1097
Abstract
Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression... (More)
Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent.Journal of Investigative Dermatology accepted article preview online, 18 December 2014. doi:10.1038/jid.2014.528. (Less)
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Contribution to journal
publication status
published
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in
Journal of Investigative Dermatology
volume
135
issue
4
pages
1089 - 1097
publisher
Nature Publishing Group
external identifiers
  • pmid:25521456
  • wos:000351188600025
  • scopus:84925442599
ISSN
1523-1747
DOI
10.1038/jid.2014.528
language
English
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yes
id
5b4f86bf-2d34-4037-b3a7-0d88c8d1ee3f (old id 4907902)
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http://www.ncbi.nlm.nih.gov/pubmed/25521456?dopt=Abstract
date added to LUP
2015-01-07 15:06:37
date last changed
2017-09-24 03:12:43
@article{5b4f86bf-2d34-4037-b3a7-0d88c8d1ee3f,
  abstract     = {Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent.Journal of Investigative Dermatology accepted article preview online, 18 December 2014. doi:10.1038/jid.2014.528.},
  author       = {Kumar, Raj and Taylor, Michael and Miao, Benchun and Ji, Zhenyu and Njauw, JennyC-N and Jönsson, Göran B and Tompers Frederick, Dennie and Tsao, Hensin},
  issn         = {1523-1747},
  language     = {eng},
  number       = {4},
  pages        = {1089--1097},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Investigative Dermatology},
  title        = {BAP1 Plays a Survival Role in Cutaneous Melanoma.},
  url          = {http://dx.doi.org/10.1038/jid.2014.528},
  volume       = {135},
  year         = {2015},
}