Journal
JOURNAL OF CELL SCIENCE
Volume 127, Issue 2, Pages 328-340Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.130161
Keywords
Spire-1; Actin; Invadosome; Src-activated 3T3; Gelatin invasion; Endothelial transmigration; Vesicular trafficking
Categories
Funding
- French Government Research Agency [MIERPV08023KSA]
- 'Fondation pour la Recherche Me 'dicale' agency [DEQ20100318279]
- EC Marie Curie integration [PIRG05-GA-2009-249158]
- FRM [DEQ20100318279]
- 'Domaines d'Interets Majeurs' DIM MALINF [R11042KK RPH11042KKA]
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Cancer cells have an increased ability to squeeze through extracellular matrix gaps that they create by promoting proteolysis of its components. Major sites of degradation are specialized micro-domains in the plasma membrane collectively named invadosomes where the Arp2/3 complex and formin proteins cooperate to spatio-temporally control actin nucleation and the folding of a dynamic Factin core. At invadosomes, proper coupling of exo-endocytosis allows polarized delivery of proteases that facilitate degradation of ECM and disruption of the cellular barrier. We investigated the contribution of the actin nucleator Spire-1 to invadosome structure and function, using Src-activated cells and cancer cells. We found that Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing Src kinase, the formin mDia1 and actin. Spire-1 interacts with the Rab3A GTPase, a key player in the regulation of exocytosis that is present at invadosomes. Finally, over-and under-expression of Spire-1 resulted in cells with an increased or decreased potential for matrix degradation, respectively, therefore suggesting a functional interplay of Spire-1 with both actin nucleation and vesicular trafficking that might impact on cell invasive and metastatic behavior.
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