title: Spire-1 contributes to the invadosome and its associated invasive properties.
abstract: 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 F-actin 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.
authors.affiliation: INSERM, U1016, Institut Cochin, 22 Rue Méchain, 75014 Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lagal
authors.forename: Marie
authors.initials: M
authors.lastname: Abrivard
authors.forename: Virginie
authors.initials: V
authors.lastname: Gonzalez
authors.forename: Audrey
authors.initials: A
authors.lastname: Perazzi
authors.forename: Sonam
authors.initials: S
authors.lastname: Popli
authors.forename: Elodie
authors.initials: E
authors.lastname: Verzeroli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tardieux
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D000080865:Formins; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D020826:rab3A GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; C000592292:SPIRE1 protein, human; C493004:Spire1 protein, mouse; D019061:src-Family Kinases; D020826:rab3A GTP-Binding Protein
keywords: Actin; Endothelial transmigration; Gelatin invasion; Invadosome; Spire-1; Src-activated 3T3; Vesicular trafficking