P-cadherin counteracts myosin II-B function: implications in melanoma progression.
BACKGROUND
Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules


RESULTS
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.


CONCLUSIONS
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 cells.
Jacobs
Koen
K
Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Ghent University, De Pintelaan 185, Ghent 9000, Belgium.
Van Gele
Mireille
M
Forsyth
Ramses
R
Brochez
Lieve
L
Vanhoecke
Barbara
B
De Wever
Olivier
O
Bracke
Marc
M
D000199:Actins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
D000199:Actins; D015820:Cadherins; D034741:RNA, Small Interfering; D024501:Nonmuscle Myosin Type IIB