BAP1 Plays a Survival Role in Cutaneous Melanoma.

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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; Tompers Frederick, Dennie; Tsao, Hensin.

In: Journal of Investigative Dermatology, Vol. 135, No. 4, 2015, p. 1089-1097.

Research output: Contribution to journalArticle

Harvard

Kumar, R, Taylor, M, Miao, B, Ji, Z, Njauw, J-N, Jönsson, GB, Tompers Frederick, D & Tsao, H 2015, 'BAP1 Plays a Survival Role in Cutaneous Melanoma.', Journal of Investigative Dermatology, vol. 135, no. 4, pp. 1089-1097. https://doi.org/10.1038/jid.2014.528

APA

Kumar, R., Taylor, M., Miao, B., Ji, Z., Njauw, J-N., Jönsson, G. B., ... Tsao, H. (2015). BAP1 Plays a Survival Role in Cutaneous Melanoma. Journal of Investigative Dermatology, 135(4), 1089-1097. https://doi.org/10.1038/jid.2014.528

CBE

Kumar R, Taylor M, Miao B, Ji Z, Njauw J-N, Jönsson GB, Tompers Frederick D, Tsao H. 2015. BAP1 Plays a Survival Role in Cutaneous Melanoma. Journal of Investigative Dermatology. 135(4):1089-1097. https://doi.org/10.1038/jid.2014.528

MLA

Vancouver

Author

Kumar, Raj ; Taylor, Michael ; Miao, Benchun ; Ji, Zhenyu ; Njauw, JennyC-N ; Jönsson, Göran B ; Tompers Frederick, Dennie ; Tsao, Hensin. / BAP1 Plays a Survival Role in Cutaneous Melanoma. In: Journal of Investigative Dermatology. 2015 ; Vol. 135, No. 4. pp. 1089-1097.

RIS

TY - JOUR

T1 - BAP1 Plays a Survival Role in Cutaneous Melanoma.

AU - Kumar, Raj

AU - Taylor, Michael

AU - Miao, Benchun

AU - Ji, Zhenyu

AU - Njauw, JennyC-N

AU - Jönsson, Göran B

AU - Tompers Frederick, Dennie

AU - Tsao, Hensin

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1038/jid.2014.528

DO - 10.1038/jid.2014.528

M3 - Article

VL - 135

SP - 1089

EP - 1097

JO - Advances in biology of skin

T2 - Advances in biology of skin

JF - Advances in biology of skin

SN - 1523-1747

IS - 4

ER -