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Sci. Signal., 4 May 2010
Vol. 3, Issue 120, p. ra35
Crossing the Basement Membrane
The basement membrane is a fibrous, sheet-like layer of the extracellular matrix located underneath epithelial or endothelial cell layers. Cell invasion through basement membranes is required during development and also during metastasis, when tumor cells leave their tissue of origin and enter lymphatic or blood vessels to migrate to secondary sites. During development of the nematode Caenorhabditis elegans, a specialized gonadal cell known as the anchor cell invades the gonadal and ventral epidermal basement membranes to initiate the formation of the female reproductive tract. Matus et al. identified and characterized genes encoding factors that promoted the ability of the anchor cell to invade basement membranes in C. elegans, most of which had not been previously implicated in cell invasion. Two of these genes, cct-5 (encoding a member of a chaperonin complex) and lit-1 (encoding a NEMO-like kinase), have human orthologs that, when knocked down in breast or colon carcinoma cells, prevented basement membrane invasion in an ex vivo system. Thus, the pro-invasive genes identified in this nematode screen could be therapeutically targeted in the treatment of metastatic cancer.
Citation: D. Q. Matus, X. Y. Li, S. Durbin, D. Agarwal, Q. Chi, S. J. Weiss, D. R. Sherwood, In Vivo Identification of Regulators of Cell Invasion Across Basement Membranes. Sci. Signal.3, ra35 (2010).