AURKA Overexpression Is Driven by FOXM1 and MAPK/ERK Activation in Melanoma Cells Harboring BRAF or NRAS Mutations: Impact on Melanoma Prognosis and Therapy.
These findings could bear significant implications for the application and the success of anti-AURKA approaches that have already entered phase-II clinical trials for human melanoma.
Further found that miR-137 reduced AURKA expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens.
We combined treatment with an aurora kinase A inhibitor, MLN8237, with agents that activate death receptors (Apo2L/TRAIL or death receptor 5 agonists) and monitored the ability of this treatment to induce tumor apoptosis and melanoma tumor regression using human cell lines and patient-derived xenograft (PDX) mouse models.
Genes deregulated at the DNA and mRNA level included well-known cancer genes partly already linked to melanoma (RAS genes, PTEN, AURKA, MAPK inhibitors Sprouty/Spred), but also novel candidates like SIPA1 (a Rap1GAP).
To refine the region of 20q amplification and to identify potential candidate genes involved in melanoma or even in melanoma progression from these regions, we combined fluorescence in-situ hybridization with MYBL2, ZNF217, CYP24 and STK6 specific probes (chromosomal region 20q13.1-q13.2) with high-throughput tissue microarray consisting of 280 primary melanomas and melanoma metastases.