FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential

Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly...

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Bibliographic Details
Published in:Cell death & disease 2013-04, Vol.4 (4), p.e578-e578
Main Authors: Romano, S, Staibano, S, Greco, A, Brunetti, A, Nappo, G, Ilardi, G, Martinelli, R, Sorrentino, A, Di Pace, A, Mascolo, M, Bisogni, R, Scalvenzi, M, Alfano, B, Romano, M F
Format: Article
Language:English
Subjects:
Animals
Biomarkers - metabolism
Cell Line, Tumor
Cell Movement
Epithelial-Mesenchymal Transition - genetics
Gene Expression Regulation, Neoplastic
Humans
Intermediate Filament Proteins - genetics
Intermediate Filament Proteins - metabolism
Melanoma - genetics
Melanoma - metabolism
Melanoma - pathology
Mice
Neoplasm Invasiveness
Neoplasms, Experimental
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Nestin
Original
RNA, Small Interfering - genetics
Signal Transduction
Skin Neoplasms - genetics
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Tacrolimus Binding Proteins - antagonists & inhibitors
Tacrolimus Binding Proteins - genetics
Tacrolimus Binding Proteins - metabolism
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Summary:Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance. We hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion. In addition, FKBP51 induced some melanoma stem cell (MCSC) genes. Purified MCSCs expressed high EMT genes levels, suggesting that genetic programs of EMT and MCSCs overlap. Immunohistochemistry of samples from patients showed intense FKBP51 nuclear signal and cytoplasmic positivity for the stem cell marker nestin in extravasating melanoma cells and metastatic brains. In addition, FKBP51 targeting by small interfering RNA (siRNA) prevented the massive metastatic substitution of liver and lung in a mouse model of experimental metastasis. The present study provides evidence that the genetic programs of cancer stemness and invasiveness overlap in melanoma, and that FKBP51 plays a pivotal role in sustaining such a program.
ISSN:2041-4889
2041-4889
DOI:10.1038/cddis.2013.109