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Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma

På svenska

Author

  • Ramin Massoumi
  • Silke Kuphal
  • Claus Hellerbrand
  • Bodo Haas
  • Peter Wild
  • Thilo Spruss
  • Alexander Pfeifer
  • Reinhard Faessler
  • Anja K. Bosserhoff

Summary, in English

High malignancy and early metastasis are hallmarks of melanoma. Here, we report that the transcription factor Snail1 inhibits expression of the tumor suppressor CYLD in melanoma. As a direct consequence of CYLD repression, the protooncogene BCL-3 translocates into the nucleus and activates Cyclin D1 and N-cadherin promoters, resulting in proliferation and invasion of melanoma cells. Rescue of CYLD expression in melanoma cells reduced proliferation and invasion in vitro and tumor growth and metastasis in vivo. Analysis of a tissue microarray with primary melanomas from patients revealed an inverse correlation of Snail1 induction and loss of CYLD expression. Importantly, tumor thickness and progression-free and overall survival inversely correlated with CYLD expression. Our data suggest that Snail1-mediated suppression of CYLD plays a key role in melanoma malignancy.

Publishing year

2009

Language

English

Pages

221-232

Publication/Series

Journal of Experimental Medicine

Volume

206

Issue

1

Document type

Journal article

Publisher

Rockefeller University Press

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Cell Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1540-9538