Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma

Ashani T. Weeraratna, Yuan Jiang, Galen Hostetter, Kevin Rosenblatt, Paul Duray, Michael Bittner, Jeffrey M. Trent

Research output: Contribution to journalArticlepeer-review

Abstract

Gene expression profiling identified human melanoma cells demonstrating increased cell motility and invasiveness. The gene WNT5A best determined in vitro invasive behavior. Melanoma cells were transfected with vectors constitutively overexpressing Wnt5a. Consistent changes included actin reorganization and increased cell adhesion. No increase in β-catenin expression or nuclear translocation was observed. There was, however, a dramatic increase in activated PKC. In direct correlation with Wnt5a expression and PKC activation, there was an increase in melanoma cell invasion. Blocking this pathway using antibodies to Frizzled-5, the receptor for Wnt5a, inhibited PKC activity and cellular invasion. Furthermore, Wnt5a expression in human melanoma biopsies directly correlated to increasing tumor grade. These observations support a role for Wnt5a in human melanoma progression.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalCancer cell
Volume1
Issue number3
DOIs
StatePublished - Apr 2002

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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