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.