P-cadherin counteracts myosin II-B function: implications in melanoma progression

In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE) and the non-invasive P-cadherin over-expression variant (BLM P-cad). Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules.Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cellsCutaneous melanoma, an aggressive cancer type originating from melanocytes in the human skin, is characterized as an invasive and commonly metastasizing tumor which is the major cause of death of melanoma patients [1,2] Normal cutaneous melanocytes form cell-cell contacts with adjacent keratinocytes, providing a molecular anchor by which melanocytes participate in the normal function and architecture of the human skin. Malignant transformation of melanocytes is featured by downregulation of cell-cell adhesion molecules like E- and P-cadherin, resulting in the loss of keratinocyte-mediated growth and motility control [3,4]. Concomitant with these changes, melanoma cells often undergo a phenomenon, referred to as epithelial-to-mesenchymal transition (EMT), and obtain a migratory and protease-producing phenotype, leading to invasion and the formation of distant metastasis [5,6]. P-cadherin is a calcium-dependent cell-cell adhesion molecule belonging to the cadherin superfamily which comprises transmembrane proteins grouped by the presence of one or more cadherin repeats