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

Massoumi, Ramin LU ; Kuphal, Silke; Hellerbrand, Claus; Haas, Bodo; Wild, Peter; Spruss, Thilo; Pfeifer, Alexander; Faessler, Reinhard and Bosserhoff, Anja K. (2009) In Journal of Experimental Medicine 206(1). p.221-232
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
206
issue
1
pages
221 - 232
publisher
Rockefeller University Press
external identifiers
  • wos:000266008300022
  • scopus:60549102324
ISSN
1540-9538
DOI
10.1084/jem.20082044
language
English
LU publication?
yes
id
349066d9-4b2b-44e6-9ac4-6aef72309d32 (old id 1425957)
date added to LUP
2009-06-26 14:24:15
date last changed
2017-11-12 03:33:59
@article{349066d9-4b2b-44e6-9ac4-6aef72309d32,
  abstract     = {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.},
  author       = {Massoumi, Ramin and Kuphal, Silke and Hellerbrand, Claus and Haas, Bodo and Wild, Peter and Spruss, Thilo and Pfeifer, Alexander and Faessler, Reinhard and Bosserhoff, Anja K.},
  issn         = {1540-9538},
  language     = {eng},
  number       = {1},
  pages        = {221--232},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma},
  url          = {http://dx.doi.org/10.1084/jem.20082044},
  volume       = {206},
  year         = {2009},
}