GSK-3 promotes cell survival, growth, and PAX3 levels in human melanoma cells

Jennifer D. Kubic, Joseph B. Mascarenhas, Takumi Iizuka, Don Wolfgeher, Deborah Lang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

GSK-3 is a serine/threonine kinase involved in a diverse range of cellular processes. GSK-3 exists in two isoforms, GSK-3α and GSK-3β, which possess some functional redundancy but also play distinct roles depending on developmental and cellular context. In this article, we found that GSK-3 actively promoted cell growth and survival in melanoma cells, and blocking this activity with small-molecule inhibitor SB216763 or gene-specific siRNA decreased proliferation, increased apoptosis, and altered cellular morphology. These alterations coincided with loss of PAX3, a transcription factor implicated in proliferation, survival, and migration of developing melanoblasts. We further found that PAX3 directly interacted with and was phosphorylated in vitro on a number of residues by GSK-3β. In melanoma cells, direct inhibition of PAX3 lead to cellular changes that paralleled the response to GSK-3 inhibition. Maintenance of PAX3 expression protected melanoma cells from the anti-tumor effects of SB216763. These data support a model wherein GSK-3 regulates proliferation and morphology of melanoma through phosphorylation and increased levels of PAX3.

Original languageEnglish (US)
Pages (from-to)1065-1076
Number of pages12
JournalMolecular Cancer Research
Volume10
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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