Cytoskeleton Dynamics: Actin in Cell Invasion

Abstract

Basement membrane (BM) is a dense sheet of specialised extracellular matrix that separates epithelial layers of cells from the underlying tissue. The penetration of cells through BM barriers, called ‘invasion’, is an important process during normal tissue development and in cancer metastasis. To enable invasion, the cell adopts different shapes and creates different protrusive structures powered mainly by actin cytoskeleton dynamics. However, the exact cytoskeletal strategy that the cell uses to cross the physical BM barrier depends on the physiological context and the physical environment, as observed by examining actin structures in invading cancer and immune cells, and in cells that invade during developmental processes such as angiogenesis and anchor cell invasion in Caenorhabditis elegans.

Key Concepts

  • Actin polymerisation and actomyosin contraction can generate cell shape changes such as protrusions.
  • Different actin‐binding proteins produce protrusions of different architecture and function.
  • Shape changes and protrusions are necessary for cell invasion across basement membrane barriers.
  • Cell invasion is observed in pathological and normal developmental contexts.
  • The actin dynamics strategy employed by an invading cell depends on the environment and the physiological context.

Keywords: cell invasion; actin; myosin; podosome; invadopodium; bleb; anchor cell invasion; angiogenesis

Figure 1. Actin biochemistry in invadopodia. Scheme of a hypothetical invadopodium, summarising all actin‐binding proteins reported to be present in invasive structures in different contexts. The lipid bilayer of the cell membrane is represented by a thick grey line. Actin filaments are represented in orange, with barbed ends labelled ‘b.e.’ and pointed ends labelled ‘p.e.’.
Figure 2. Anchor cell invasion in C. elegans. (a) DIC and epifluorescence images of AC invasion in an early stage (before BM penetration) and in a late stage (BM effaced), showing the accumulation of filamentous actin at the AC/BM interface just before BM breaching and the actin‐rich protrusion that forms during invasion. Actin in the AC is labelled with Life act‐GFP and BM with mCherry‐laminin. Bar 5 µm. Rodrigo Cáceres, unpublished, 2016. (b) Scheme of what is known about actin dynamics in the AC. Actin filaments are represented in orange.
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Further Reading

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Cáceres, Rodrigo, and Plastino, Julie(Apr 2017) Cytoskeleton Dynamics: Actin in Cell Invasion. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001254.pub2]