BAP1 Plays a Survival Role in Cutaneous Melanoma.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Raj Kumar
  • Michael Taylor
  • Benchun Miao
  • Zhenyu Ji
  • JennyC-N Njauw
  • Göran B Jönsson
  • Dennie Tompers Frederick
  • Hensin Tsao
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Dermatologi och venereologi
Originalspråkengelska
Sidor (från-till)1089-1097
TidskriftJournal of Investigative Dermatology
Volym135
Utgivningsnummer4
StatusPublished - 2015
PublikationskategoriForskning
Peer review utfördJa