Loss of Klotho during melanoma progression leads to increased filamin cleavage, increased Wnt5A expression, and enhanced melanoma cell motility

Tura C. Camilli, Mai Xu, Michael P. O'Connell, Bonnie Chien, Brittany P. Frank, Sarah Subaran, Fred E. Indig, Patrice J. Morin, Stephen M. Hewitt, Ashani T. Weeraratna

Research output: Contribution to journalArticle

Abstract

We have previously shown that Wnt5A-mediated signaling can promote melanoma metastasis. It has been shown that Wnt signaling is antagonized by the protein Klotho, which has been implicated in aging. We show here that in melanoma cells, expressions of Wnt5A and Klotho are inversely correlated. In the presence of recombinant Klotho (rKlotho), we show that Wnt5A internalization and signaling is decreased in high Wnt5A-expressing cells. Moreover, in the presence of rKlotho, we observe an increase in Wnt5A remaining in the medium, coincident with an increase in sialidase activity, and decrease in syndecan expression. These effects can be inhibited using a sialidase inhibitor. In addition to its effects on Wnt5A internalization, we also demonstrate that Klotho decreases melanoma cell invasive potential by a second mechanism that involves the inhibition of calpain and a resultant decrease in filamin cleavage, which we demonstrate is critical for melanoma cell motility. John Wiley & Sons A/S. Published 2010. This article is a US Government work and is in the public domain in the USA.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalPigment Cell and Melanoma Research
Volume24
Issue number1
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • Klotho
  • Melanoma
  • Sialidase
  • Syndecan
  • Wnt5A

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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