title: Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia.
abstract: 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.
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Isabel
authors.initials: I
authors.lastname: Van Audenhove
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Majken
authors.initials: M
authors.lastname: Denert
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Ciska
authors.initials: C
authors.lastname: Boucherie
authors.affiliation: Basic Medical Science, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Pieters
authors.affiliation: Basic Medical Science, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Cornelissen
authors.affiliation: From the Departments of Biochemistry and jan.gettemans@ugent.be.
authors.forename: Jan
authors.initials: J
authors.lastname: Gettemans
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; C047262:LCP1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C020324:fascin
keywords: L-plastin; actin; cancer biology; cell invasion; fascin; filopodia; invadopodia; molecular dynamics; nanobodies