The inhibition of invasion of human melanoma cells through N-cadherin knock-down

Abstract

N-cadherin seems to promote cell migration and invasion in many types of cancers. The object of this study is recognition of the possible role of N-cadherin and selected downstream protein kinases: PI3K, ERK1/2, and mTOR in cell invasion in malignant melanoma. Melanoma cells were transfected with the small interfering RNA (siRNA) that targets human N-cadherin gene (CDH2). Inhibitors LY294002 (PI3K), U0126 (ERK1/2), and everolimus (mTOR) were used to inhibit selected kinases of signalling pathways. In vitro cell invasion was studied using Matrigel and an analysis of matrix metalloproteinases MMP-2 and MMP-9 activity by gelatinase zymogram assay. Treatment of melanoma cell with either siRNA against N-cadherin or protein kinase inhibitors led to significantly decreased MMPs expression and activity, as well as diminished invasion. Both the current and the former results suggest that activation of PI3/AKT, mTOR, and ERK kinase, following N-cadherin expression, contributes not only to increased proliferation but also invasive potential of melanoma cells. The results also indicate that N-cadherin, as well as the studied kinases, should be considered as a potential target in melanoma therapy.