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The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance
Author(s) -
Schittek Birgit,
Psenner Karin,
Sauer Birgit,
Meier Friedegund,
Iftner Thomas,
Garbe Claus
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22512
Subject(s) - melanoma , cancer research , downregulation and upregulation , cyclin d1 , cell growth , biology , apoptosis , metastasis , pathology , cancer , medicine , cell cycle , gene , biochemistry , genetics
In previous studies we identified the transcription/translation factor Y‐box‐binding protein (YB‐1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB‐1 expression correlates with melanoma progression in vitro and in vivo , we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB‐1 expression is increased in melanoma cells in vitro and in vivo and that YB‐1 is translocated into the nucleus in invasive and metastatic melanoma cells. To reveal the functional role of YB‐1 in melanoma progression we achieved a stable downregulation of YB‐1 using shRNA in metastatic melanoma cells. Interestingly, YB‐1 downregulation resulted in a pronounced reduced rate of proliferation and an increased rate of apoptotic cell death. In addition, migration and invasion of melanoma cells in monolayer and in a three‐dimensional skin reconstruct in vitro was significantly reduced. These effects were accompanied by downregulation of genes involved in proliferation, survival and migration/invasion of melanoma cells such as MMP‐2, bcl‐2, Cyclin D1, p53 and p16INK4A. Furthermore, melanoma cells with a reduced YB‐1 expression showed a decreased resistance to the chemotherapeutic agents cisplatin and etoposide. These data suggest that YB‐1 is involved in malignant transformation of melanocytes and contributes to the stimulation of proliferation, tumor invasion, survival and chemoresistance. Thus, YB‐1 may be a promising molecular target in melanoma therapy. © 2007 Wiley‐Liss, Inc.