Inhibition of the Proprotein Convertases Represses the Invasiveness of Human Primary Melanoma Cells with Altered p53, CDKN2A and N-Ras Genes

The CDKN2A locus codes for the tumor suppressors p16 and ARF that regulate cell cycle progression, DNA repair and cell invasion via activating pRb, and the p53 pathway via inhibiting the activity of MDM2, respectively. Mutations or deletions of the CDKN2A gene result in altered MMPs/TIMPs and/or uPA/uPAR/PAI-1 expression and activity, which in turn lead to tumor cell invasion. The Ras gene is important for regulating the ERK activity, and hence expression of MMPs and uPA/uPAR. An activating mutation in the Ras gene can result in uncontrolled activity of MMPs and the urokinase system, which can lead to increased melanoma invasion. Blockade of PCs activity can reduce the expression and/or generation of active MMPs, uPA and uPAR leading to reduced tumor cells invasiveness. The asterisks indicate altered genes.

Publication

Inhibition of the Proprotein Convertases Represses the Invasiveness of Human Primary Melanoma Cells with Altered p53, CDKN2A and N-Ras Genes. (2010) Claude Lalou, et al. PLoS One. 2010;5(4):e9992. Figure: F7. All organisms Drosophila melanogaster Homo sapiens

Disease mentions