RGD Reference Report - Amlexanox reversibly inhibits cell migration and proliferation and induces the Src-dependent disassembly of actin stress fibers in vitro. - Rat Genome Database

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Amlexanox reversibly inhibits cell migration and proliferation and induces the Src-dependent disassembly of actin stress fibers in vitro.

Authors: Landriscina, M  Prudovsky, I  Mouta Carreira, C  Soldi, R  Tarantini, F  Maciag, T 
Citation: Landriscina M, etal., J Biol Chem. 2000 Oct 20;275(42):32753-62.
RGD ID: 2316111
Pubmed: PMID:10921913   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M002336200   (Journal Full-text)

Amlexanox binds S100A13 and inhibits the release of fibroblast growth factor 1 (FGF1). Because members of the S100 gene family are known to be involved with the function of the cytoskeleton, we examined the ability of amlexanox to modify the cytoskeleton and report that amlexanox induces a dramatic reduction in the presence of actin stress fibers and the appearance of a random, non-oriented distribution of focal adhesion sites. Correspondingly, amlexanox induces the complete and reversible non-apoptotic inhibition of cell migration and proliferation, and although amlexanox does not induce either the down-regulation of F-actin levels or the depolymerization of actin filaments, it does induce the tyrosine phosphorylation of cortactin, a Src substrate known to regulate actin bundling. In addition, a dominant negative form of Src is able to partially rescue cells from the effect of amlexanox on both the actin cytoskeleton and cell migration. In contrast, the inhibition of cell proliferation by amlexanox correlates with the inhibition of cyclin D1 expression without interference of the receptor tyrosine kinase/mitogen-activated protein kinase signaling pathway. Last, the ability of amlexanox to inhibit FGF1 release is reversible and correlates with the restoration of the actin cytoskeleton, suggesting a role for the actin cytoskeleton in the FGF1 release pathway.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell population proliferation  IMP 2316111 RGD 
regulation of cell shape  IMP 2316111 RGD 

Objects Annotated

Genes (Rattus norvegicus)
S100a13  (S100 calcium binding protein A13)


Additional Information