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Sci. Signal., 4 May 2010
Vol. 3, Issue 120, p. ra35
[DOI: 10.1126/scisignal.2000654]

RESEARCH ARTICLES

In Vivo Identification of Regulators of Cell Invasion Across Basement Membranes

David Q. Matus1, Xiao-Yan Li2,3, Sarah Durbin1, Daniel Agarwal1*, Qiuyi Chi1, Stephen J. Weiss2,3, and David R. Sherwood1{dagger}

1 Biology Department, Duke University, Durham, NC 27708, USA.
2 Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
3 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.

* Present address: Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.

Abstract: Cell invasion through basement membranes during development, immune surveillance, and metastasis remains poorly understood. To gain further insight into this key cellular behavior, we performed an in vivo screen for regulators of cell invasion through basement membranes, using the simple model of Caenorhabditis elegans anchor cell invasion, and identified 99 genes that promote invasion, including the genes encoding the chaperonin complex cct. Notably, most of these genes have not been previously implicated in invasive cell behavior. We characterized members of the cct complex and 11 other gene products, determining the distinct aspects of the invasive cascade that they regulate, including formation of a specialized invasive cell membrane and its ability to breach the basement membrane. RNA interference–mediated knockdown of the human orthologs of cct-5 and lit-1, which had not previously been implicated in cell invasion, reduced the invasiveness of metastatic carcinoma cells, suggesting that a conserved genetic program underlies cell invasion. These results increase our understanding of the genetic underpinnings of cell invasion and also provide new potential therapeutic targets to limit this behavior.

{dagger} To whom correspondence should be addressed. E-mail: david.sherwood{at}duke.edu

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).

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