S100P dissociates myosin IIA filaments and focal adhesion sites to reduce cell adhesion and enhance cell migration


S100 proteins promote cancer cell migration and metastasis. To investigate their roles in the process of migration we have constructed inducible systems for S100P in rat mammary and human HeLa cells that show a linear relationship between its intracellular levels and cell migration. S100P, like S100A4, differentially interacts with the isoforms of nonmuscle myosin II (NMIIA, K(d) = 0.5 µm; IIB, K(d) = 8 µm; IIC, K(d) = 1.0 µm). Accordingly, S100P dissociates NMIIA and IIC filaments but not IIB in vitro. NMIIA knockdown increases migration in non-induced cells and there is no further increase upon induction of S100P, whereas NMIIB knockdown reduces cell migration whether or not S100P is induced. NMIIC knockdown does not affect S100P-enhanced cell migration. Further study shows that NMIIA physically interacts with S100P in living cells. In the cytoplasm, S100P occurs in discrete nodules along NMIIA-containing filaments. Induction of S100P causes more peripheral distribution of NMIIA filaments. This change is paralleled by a significant drop in vinculin-containing, actin-terminating focal adhesion sites (FAS) per cell. The induction of S100P, consequently, causes significant reduction in cellular adhesion. Addition of a focal adhesion kinase (FAK) inhibitor reduces disassembly of FAS and thereby suppresses S100P-enhanced cell migration. In conclusion, this work has demonstrated a mechanism whereby the S100P-induced dissociation of NMIIA filaments leads to a weakening of FAS, reduced cell adhesion, and enhanced cell migration, the first major step in the metastatic cascade.

Publication DOI: https://doi.org/10.1074/jbc.M112.349787
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: This research was originally published in Journal of biological chemistry. Du, M, Wang, G, Ismail, TM, Gross, S, Fernig, DG, Barraclough, R & Rudland, PS. S100P dissociates myosin IIA filaments and focal adhesion sites to reduce cell adhesion and enhance cell migration. Journal of biological chemistry. 2012; Vol 287:15330-15344 © the American Society for Biochemistry and Molecular Biology
Uncontrolled Keywords: cell adhesion,S100 proteins,myosin,metastasis,cell migration,Biochemistry,Cell Biology,Molecular Biology
Publication ISSN: 1083-351X
Last Modified: 18 Jun 2024 07:09
Date Deposited: 22 Jun 2012 12:20
Full Text Link: http://www.jbc. ... nt/287/19/15330
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2012-05-04
Published Online Date: 2012-03-06
Authors: Du, Min
Wang, Guozheng
Ismail, Thamir M.
Gross, Stephane (ORCID Profile 0000-0002-0867-8866)
Fernig, David G.
Barraclough, Roger
Rudland, Philip S.



Version: Draft Version

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