In vivo identification of regulators of cell invasion across basement membranes.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Matus, DQ; Li, X-Y; Durbin, S; Agarwal, D; Chi, Q; Weiss, SJ; Sherwood, DR

Published Date

  • May 4, 2010

Published In

Volume / Issue

  • 3 / 120

Start / End Page

  • ra35 -

PubMed ID

  • 20442418

Pubmed Central ID

  • 20442418

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

International Standard Serial Number (ISSN)

  • 1945-0877

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2000654

Language

  • eng