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

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.

authors

Camilli TC,Xu M,O'Connell MP,Chien B,Frank BP,Subaran S,Indig FE,Morin PJ,Hewitt SM,Weeraratna AT

doi

10.1111/j.1755-148X.2010.00792.x

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

175-86

issue

1

eissn

1755-1471

issn

1755-148X

journal_volume

24

pub_type

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