Cell Biology

Breaking Out

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Science  28 May 2010:
Vol. 328, Issue 5982, pp. 1077
DOI: 10.1126/science.328.5982.1077-b

The basement membrane is a dense extracellular meshwork of collagens, glycoproteins, and proteoglycans that surrounds most tissues in metazoans, providing structural support and regulating cell function. It acts as a barrier to the passive diffusion of molecules larger than 50 nm, but some cells possess the ability to cross the basement membrane, which is important during development, when new tissues are being formed, and during wound healing. Metastasis of epithelial tumors, which often is lethal, also requires the tumor cells first to cross a basement membrane in order to enter the blood or lymphatic vessels and thence to spread to distal sites. Thus, understanding how cell invasion occurs in vivo is important for understanding both development and disease.

During Caenorhabditis elegans larval development, anchor cells initiate uterine-vulval contact in response to cues from underlying vulval precursor cells by breaching the obstructing basement membrane. Matus et al. have combined this in vivo model system with a comprehensive RNAi screen to identify 99 genes involved in cell invasion, some of which were already known to be involved, as well as genes not previously linked to this process. Follow-up analysis of a subset of genes revealed roles in distinct stages of invasion, including the establishment of the specialized invasive membrane in the invading cell and the removal of basement membrane. Many of these genes are conserved in humans, and two of them were found to be required for the invasion of human breast and colon cancer cells in an ex vivo model, and are thus potential targets for limiting cancer metastasis.

Sci. Signal. 3, ra35 (2010).

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