Details

Autor(en) / Beteiligte

• Jalili, Ahmad
• Moser, Anna
• Pashenkov, Mikhail
• Wagner, Christine
• Pathria, Gaurav
• Borgdorff, Viola
• Gschaider, Melanie
• Stingl, Georg
• Ramaswamy, Sridhar
• Wagner, Stephan N.

Titel

Polo-Like Kinase 1 Is a Potential Therapeutic Target in Human Melanoma

Ist Teil von

• Journal of investigative dermatology, 2011-09, Vol.131 (9), p.1886-1895

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Exploration of the human melanoma cell-cycle pathway can lead to identification of new therapeutic targets. By gene set enrichment analysis, we identified the cell-cycle pathway and its member polo-like kinase 1 (Plk-1) to be significantly overexpressed in primary melanomas and in melanoma metastases. In vitro expression of Plk-1 was peaked at the G2/M phase of the cell cycle. Plk-1 knockdown/inhibition led to induction of apoptosis, which was caspase-3/8-dependent and p53-independent, and involved BID and Bcl-2 proteins. Comparative genomic hybridization/single-nucleotide polymorphism arrays showed no genetic alteration in the Plk-1 locus. Previous suggestions and significant enrichment of the mitogen-activated protein kinase (MAPK) signaling pathway pointed to potential regulation of Plk-1 by MAPK signaling. Inhibition of this pathway resulted in decreased Plk-1 expression as a consequence of G1 cell-cycle arrest rather than direct regulation of Plk-1. Inhibition of MAPK and Plk-1 had an additive effect on reduced cell viability. This study shows that in human melanoma, Plk-1 expression is dynamically regulated during the cell cycle, knockdown of Plk-1 leads to apoptotic cell death, and that a combination of Plk-1 and MAPK inhibition has an additive effect on melanoma cell viability. We conclude that combined inhibition of Plk-1 and MAPK could be a potentially attractive strategy in melanoma therapy.