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Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia.
J Biol Chem. 2016 Apr 22; 291(17):9148-60.JB

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+Show Affiliations

From the Departments of Biochemistry and.From the Departments of Biochemistry and.From the Departments of Biochemistry and.Basic Medical Science, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.Basic Medical Science, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.From the Departments of Biochemistry and jan.gettemans@ugent.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26945069

Citation

Van Audenhove, Isabel, et al. "Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia." The Journal of Biological Chemistry, vol. 291, no. 17, 2016, pp. 9148-60.
Van Audenhove I, Denert M, Boucherie C, et al. Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. J Biol Chem. 2016;291(17):9148-60.
Van Audenhove, I., Denert, M., Boucherie, C., Pieters, L., Cornelissen, M., & Gettemans, J. (2016). Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. The Journal of Biological Chemistry, 291(17), 9148-60. https://doi.org/10.1074/jbc.M115.706937
Van Audenhove I, et al. Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. J Biol Chem. 2016 Apr 22;291(17):9148-60. PubMed PMID: 26945069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia. AU - Van Audenhove,Isabel, AU - Denert,Majken, AU - Boucherie,Ciska, AU - Pieters,Leen, AU - Cornelissen,Maria, AU - Gettemans,Jan, Y1 - 2016/03/04/ PY - 2015/12/07/received PY - 2016/3/6/entrez PY - 2016/3/6/pubmed PY - 2016/11/4/medline KW - L-plastin KW - actin KW - cancer biology KW - cell invasion KW - fascin KW - filopodia KW - invadopodia KW - molecular dynamics KW - nanobodies SP - 9148 EP - 60 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 291 IS - 17 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/26945069/Fascin_Rigidity_and_L_plastin_Flexibility_Cooperate_in_Cancer_Cell_Invadopodia_and_Filopodia_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=26945069 DB - PRIME DP - Unbound Medicine ER -