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

Mol Cancer. 2010 Sep 22:9:255. doi: 10.1186/1476-4598-9-255.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Microscopy, Confocal
  • Nonmuscle Myosin Type IIB / genetics
  • Nonmuscle Myosin Type IIB / metabolism*
  • Polymerase Chain Reaction
  • RNA, Small Interfering
  • Tumor Cells, Cultured

Substances

  • Actins
  • Cadherins
  • RNA, Small Interfering
  • Nonmuscle Myosin Type IIB