Spire-1 a novel contributor of invadosome and associated invasive properties

Abstract

Cancer cells have gained increased abilities to squeeze through extracellular matrix gaps they contribute to 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 the Formins 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 ECM degradation and cellular barrier disruption. We investigated the contribution of the actin nucleator Spire-1 to invadosome structure and functions, using Src-activated and cancer cells. We found that Spire-1 is specifically recruited at invadosomes and is part of a multi-molecular complex containing the Src kinase, the Formin mDia1 and actin. Spire-1 interacts with the Rab3A GTPase, a key player in regulated exocytosis present at invadosomes. Finally, over and under-expression of Spire-1 entailed cells with an increase or decrease 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 behaviors.