Skeleton key for cancer metastasis

Apr 26, 2010
An actin-rich invadopodium pushes through the basement membrane (red, left), allowing the tumor cell to follow (right). Credit: Schoumacher, M., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200909113.

Cancer cells need all three of their cytoskeletons—actin, microtubules, and intermediate filaments—to metastasize, according to a study published online on April 26 in the Journal of Cell Biology.

A cancer cell in an epithelial layer is trapped unless it can force through the basement membrane, which cordons off the tissue. start to dissolve the basement membrane with enzymes that build up within extensions called invadopodia. How the different components of the cytoskeleton collaborate to spring the cell remains unclear. To find out, Danijela Vignjevic and colleagues (Institut Curie) followed as they started their breakout.

They found that a tumor cell escapes in three stages. First, stumpy protrusions dig into the basement membrane. These structures then elongate into "mature" invadopodia. Finally, the rest of the cell follows. In culture, crawling cells produce extensions that carry either bundles of actin or an actin mesh. In the cells, both forms of actin were necessary for invadopodia to form and grow. However, microtubules and intermediate filaments were only essential for invadopodia to lengthen.

The researchers suggest a model for this initial step of metastasis. Growing actin bundles push out a protrusion, which the actin mesh stabilizes as it elongates. Only if the invadopodium stretches beyond 5 microns do microtubules and intermediate filaments get involved. most likely elongate the invadopodium by delivering materials such as enzymes to the tip. Intermediate filaments, meanwhile, may brace the growing extension.

Explore further: Two-armed control of ATR, a master regulator of the DNA damage checkpoint

More information: Schoumacher, M., et al. 2010. J. Cell Biol. doi:10.1083/jcb.200909113

Provided by Rockefeller University

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