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. (2009) Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma. JOURNAL OF EXPERIMENTAL MEDICINE, 206 (1). pp. 221-232. ISSN 0022-1007, 1540-9538
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITIONS; E-CADHERIN EXPRESSION; TRANSCRIPTION FACTOR SNAIL; INHIBITING ACTIVITY; SIGNALING PATHWAY; UP-REGULATION; HUMAN COLON; CELLS; MIGRATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Oct 2020 09:06 |
| Last Modified: | 07 Oct 2020 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29572 |
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