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Loss of Klotho during melanoma progression leads to increased filamin cleavage, increased Wnt5A expression, and enhanced melanoma cell motility
Author(s) -
Camilli Tura C.,
Xu Mai,
O’Connell Michael P.,
Chien Bonnie,
Frank Brittany P.,
Subaran Sarah,
Indig Fred E.,
Morin Patrice J.,
Hewitt Stephen M.,
Weeraratna Ashani T.
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00792.x
Subject(s) - melanoma , internalization , motility , calpain , klotho , filamin , wnt signaling pathway , microbiology and biotechnology , cancer research , wnt5a , signal transduction , chemistry , cell , biology , endocrinology , biochemistry , enzyme , cytoskeleton , kidney
Summary 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.