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Fascin rigidity and L-plastin flexibility cooperate in cancer cell invadopodia and filopodia

Isabel Van Audenhove (UGent), Majken Denert (UGent), Ciska Boucherie (UGent), Leen Pieters (UGent), Maria Cornelissen (UGent) and Jan Gettemans (UGent)
(2016) JOURNAL OF BIOLOGICAL CHEMISTRY. 291(17). p.9148-9160
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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.
Keywords
ACTIN-BUNDLING PROTEINS, AMYLOIDOSIS MOUSE MODEL, ARCHITECTURE, MACROPHAGES, NANOBODIES, INVASION, MECHANISM, ADHESION, METASTASIS, PHOSPHORYLATION

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Chicago
Van Audenhove, Isabel, Majken Denert, Ciska Boucherie, Leen Pieters, Maria Cornelissen, and Jan Gettemans. 2016. “Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia.” Journal of Biological Chemistry 291 (17): 9148–9160.
APA
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. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(17), 9148–9160.
Vancouver
1.
Van Audenhove I, Denert M, Boucherie C, Pieters L, Cornelissen M, Gettemans J. Fascin rigidity and L-plastin flexibility cooperate in cancer cell invadopodia and filopodia. JOURNAL OF BIOLOGICAL CHEMISTRY. 2016;291(17):9148–60.
MLA
Van Audenhove, Isabel, Majken Denert, Ciska Boucherie, et al. “Fascin Rigidity and L-plastin Flexibility Cooperate in Cancer Cell Invadopodia and Filopodia.” JOURNAL OF BIOLOGICAL CHEMISTRY 291.17 (2016): 9148–9160. Print.
@article{7244060,
  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.},
  author       = {Van Audenhove, Isabel and Denert, Majken and Boucherie, Ciska and Pieters, Leen and Cornelissen, Maria and Gettemans, Jan},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {ACTIN-BUNDLING PROTEINS,AMYLOIDOSIS MOUSE MODEL,ARCHITECTURE,MACROPHAGES,NANOBODIES,INVASION,MECHANISM,ADHESION,METASTASIS,PHOSPHORYLATION},
  language     = {eng},
  number       = {17},
  pages        = {9148--9160},
  title        = {Fascin rigidity and L-plastin flexibility cooperate in cancer cell invadopodia and filopodia},
  url          = {http://dx.doi.org/10.1074/jbc.M115.706937},
  volume       = {291},
  year         = {2016},
}

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