Role of β-catenin signaling in the anti-invasive effect of the omega-3 fatty acid DHA in human melanoma cells.

Simona Serini, Gabriella Calviello, Elena Fasano, Leonardo Celleno, Antonio Zinzi, Renata Ottes Vasconcelos, Maria Greca Riillo, Sonia Trombino, Roberta Cassano

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

12 Citazioni (Scopus)

Abstract

BACKGROUND: We previously found that docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid present at high level in fatty fish, inhibited cell growth and induced differentiation of melanoma cells in vitro by increasing nuclear β-catenin content. An anti-neoplastic role of nuclear β-catenin was suggested in melanoma, and related to the presence in the melanocyte lineage of the microphtalmia transcription factor (MITF), which interferes with the transcription of β-catenin/TCF/LEF pro-invasive target genes. OBJECTIVE: In the present work we investigated if DHA could inhibit the invasive potential of melanoma cells, and if this effect could be related to DHA-induced alterations of the Wnt/β-catenin signaling, including changes in MITF expression. METHODS: WM115 and WM266-4 human melanoma, and B16-F10 murine melanoma cell lines were used. Cell invasion was evaluated by Wound Healing and Matrigel transwell assays. Protein expression was analyzed by Western Blotting and β-catenin phosphorylation by immunoprecipitation. The role of MITF in the anti-invasive effect of DHA was analyzed by siRNA gene silencing. RESULTS: We found that DHA inhibited anchorage-independent cell growth, reduced their migration/invasion in vitro and down-regulated several Matrix Metalloproteinases (MMP: MMP-2, MT1-MMP and MMP-13), known to be involved in melanoma invasion. We related these effects to the β-catenin increased nuclear expression and PKA-dependent phosphorylation, as well as to the increased expression of MITF. CONCLUSION: The data obtained further support the potential role of dietary DHA as suppressor of melanoma progression to invasive malignancy through its ability to enhance MITF expression and PKA-dependent nuclear β-catenin phosphorylation.
Lingua originaleEnglish
pagine (da-a)149-159
Numero di pagine11
RivistaJournal of Dermatological Science
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Docosahexaenoic acid
  • Invasion
  • MITF
  • Melanoma
  • PKA
  • β-Catenin

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