Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres

Cervero, Pasquale; Himmel, Mirko; Krüger, Marcus; Linder, Stefan

doi:10.1016/j.ejcb.2012.05.005

Cited by 61 publications

(69 citation statements)

References 70 publications

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“…This was further confirmed by proteomic analysis of macrophage podosome fractions (54). Therefore, further research mainly focused on the role of L-plastin in podosomes and immune cell function (27)(28)(29).…”

Section: Fascin Guarantees Protrusion and Structural Rigidity Whereamentioning

confidence: 67%

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Audenhove¹,

Denert²,

Boucherie³

et al. 2016

Journal of Biological Chemistry

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Invadopodia and filopodia are dynamic, actin-based protrusions contributing to cancer cell migration, invasion, and metastasis. The force of actin bundles is essential for their protrusive activity. The bundling protein fascin is known to play a role in both invadopodia and filopodia. As it is more and more acknowledged that functionally related proteins cooperate, it is unlikely that only fascin bundles actin in these protrusions. Another interesting candidate is L-plastin, normally expressed in hematopoietic cells, but considered a common marker of many cancer types. We identified L-plastin as a new component of invadopodia, where it contributes to degradation and invasiveness. By means of specific, high-affinity nanobodies inhibiting bundling of fascin or L-plastin, we further unraveled their cooperative mode of action. We show that the bundlers cannot compensate for each other due to strikingly different bundling characteristics: L-plastin bundles are much thinner and less tightly packed. Composite bundles adopt an intermediate phenotype, with fascin delivering the rigidity and strength for protrusive force and structural stability, whereas L-plastin accounts for the flexibility needed for elongation. Consistent with this, elevated L-plastin expression promotes elongation and reduces protrusion density in cells with relatively lower L-plastin than fascin levels.Filopodia are finger-like protrusions coordinating movement at the cell front by "sensing" extracellular stimuli (1). Invadopodia on the other hand are formed at the ventral cell side, enabling matrix degradation by localized proteolysis (2). As both actin-based protrusions contribute to migration and invasion, they are associated with cancer metastasis (3, 4), which has also been shown in vivo (5, 6).The architecture and dynamics of filopodia and invadopodia are controlled by a broad variety of actin-binding proteins (7,8). Moreover, these regulating proteins show highly similar spatial and temporal distributions in filopodia and invadopodia (9).

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Section: Fascin Guarantees Protrusion and Structural Rigidity Whereamentioning

confidence: 67%

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Audenhove¹,

Denert²,

Boucherie³

et al. 2016

Journal of Biological Chemistry

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“…Strikingly, among the 203 components identified, 170 are new structural and regulatory members largely composed of cytoskeleton proteins, GTP-binding and GTPase factors (Cervero et al, 2012). Invadosome scaffolding relies on actin nucleation, with a tight cooperation between the Arp2/3 actin-nucleating complex and the class of formins.…”

Section: Discussionmentioning

confidence: 99%

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

Lagal

Abrivard

Gonzalez

et al. 2013

Journal of Cell Science

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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 microdomains in the plasma membrane collectively named invadosomes where the Arp2/3 complex and formin proteins cooperate to spatiotemporally 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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“…Invadopodia and podosomes (shown as circular structures in the figure) are punctate branched actin-rich structures defined, in part, by the presence of a substantial amount of actin regulatory proteins, such as the Arp2/3 complex, cortactin and N-WASp, along with TKS5, active Src kinase, tyrosine phosphorylated proteins and the proteinase MT1-MMP (Murphy and Courtneidge, 2011;Weaver, 2006). Recent proteomic studies have respectively identified ,200 putative podosome components and ,60 putative invadopodia components (Attanasio et al, 2011;Cervero et al, 2012). Although invadopodia-producing cells generally only form punctate actin structures, podosome puncta can assemble into higher-order structures, such as podosome rosettes and podosome belts (the double layer of podosomes at cell periphery).…”

Section: Introductionmentioning

confidence: 99%

Signaling inputs to invadopodia and podosomes

Hoshino

Branch

Weaver

2013

Journal of Cell Science

152

175

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SummaryRemodeling of extracellular matrix (ECM) is a fundamental cell property that allows cells to alter their microenvironment and move through tissues. Invadopodia and podosomes are subcellular actin-rich structures that are specialized for matrix degradation and are formed by cancer and normal cells, respectively. Although initial studies focused on defining the core machinery of these two structures, recent studies have identified inputs from both growth factor and adhesion signaling as crucial for invasive activity. This Commentary will outline the current knowledge on the upstream signaling inputs to invadopodia and podosomes and their role in governing distinct stages of these invasive structures. We discuss invadopodia and podosomes as adhesion structures and highlight new data showing that invadopodia-associated adhesion rings promote the maturation of already-formed invadopodia. We present a model in which growth factor stimulation leads to phosphoinositide 3-kinase (PI3K) activity and formation of invadopodia, whereas adhesion signaling promotes exocytosis of proteinases at invadopodia.

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Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres

Cited by 61 publications

References 70 publications

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia

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

Signaling inputs to invadopodia and podosomes

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