The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo.

Published

Journal Article

Though critical to normal development and cancer metastasis, how cells traverse basement membranes is poorly understood. A central impediment has been the challenge of visualizing invasive cell interactions with basement membrane in vivo. By developing live-cell imaging methods to follow anchor cell (AC) invasion in Caenorhabditis elegans, we identify F-actin-based invadopodia that breach basement membrane. When an invadopodium penetrates basement membrane, it rapidly transitions into a stable invasive process that expands the breach and crosses into the vulval tissue. We find that the netrin receptor UNC-40 (DCC) specifically enriches at the site of basement membrane breach and that activation by UNC-6 (netrin) directs focused F-actin formation, generating the invasive protrusion and the cessation of invadopodia. Using optical highlighting of basement membrane components, we further demonstrate that rather than relying solely on proteolytic dissolution, the AC's protrusion physically displaces basement membrane. These studies reveal an UNC-40-mediated morphogenetic transition at the cell-basement membrane interface that directs invading cells across basement membrane barriers.

Full Text

Duke Authors

Cited Authors

  • Hagedorn, EJ; Ziel, JW; Morrissey, MA; Linden, LM; Wang, Z; Chi, Q; Johnson, SA; Sherwood, DR

Published Date

  • June 2013

Published In

Volume / Issue

  • 201 / 6

Start / End Page

  • 903 - 913

PubMed ID

  • 23751497

Pubmed Central ID

  • 23751497

Electronic International Standard Serial Number (EISSN)

  • 1540-8140

International Standard Serial Number (ISSN)

  • 1540-8140

Digital Object Identifier (DOI)

  • 10.1083/jcb.201301091

Language

  • eng