S100A4 downregulates filopodia formation through increased dynamic instability


Cell migration requires the initial formation of cell protrusions, lamellipodia and/or filopodia, the attachment of the leading lamella to extracellular cues and the formation and efficient recycling of focal contacts at the leading edge. The small calcium binding EF-hand protein S100A4 has been shown to promote cell motility but the direct molecular mechanisms responsible remain to be elucidated. In this work, we provide new evidences indicating that elevated levels of S100A4 affect the stability of filopodia and prevent the maturation of focal complexes. Increasing the levels of S100A4 in a rat mammary benign tumor derived cell line results in acquired cellular migration on the wound healing scratch assay. At the cellular levels, we found that high levels of S100A4 induce the formation of many nascent filopodia, but that only a very small and limited number of those can stably adhere and mature, as opposed to control cells, which generate fewer protrusions but are able to maintain these into more mature projections. This observation was paralleled by the fact that S100A4 overexpressing cells were unable to establish stable focal adhesions. Using different truncated forms of the S100A4 proteins that are unable to bind to myosin IIA, our data suggests that this newly identified functions of S100A4 is myosin-dependent, providing new understanding on the regulatory functions of S100A4 on cellular migration.

Publication DOI: https://doi.org/10.4161/cam.5.5.17773
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: Goh, C, Hersch, N, Rudland, PS, Barraclough, R, Hoffmann, B & Gross, SR 2011, 'S100A4 downregulates filopodia formation through increased dynamic instability', Cell adhesion and migration, vol 5, no. 5, pp. 439-447. The journal is the original source.
Uncontrolled Keywords: cancer progression,cell migration,filopodia,focal adhesion,myosin IIA,S100A4,Cell Biology,Cellular and Molecular Neuroscience
Publication ISSN: 1933-6926
Last Modified: 03 Jan 2024 18:14
Date Deposited: 22 Jun 2012 11:56
Full Text Link: http://www.land ... /article/17773/
http://www.scop ... tnerID=8YFLogxK
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PURE Output Type: Article
Published Date: 2011-09
Authors: Goh, Connie
Hersch, Nils
Rudland, Philip S.
Barraclough, Roger
Hoffmann, Bernd
Gross, Stephane R. (ORCID Profile 0000-0002-0867-8866)



Version: Accepted Version

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