An integrin-linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization.
Cancer Cell
; 24(4): 481-98, 2013 Oct 14.
Article
in En
| MEDLINE
| ID: mdl-24035453
ABSTRACT
Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin ß1-containing, filopodium-like protrusions (FLPs), which enable them to interact productively with the surrounding extracellular matrix; this process governs the initial proliferation of these cancer cells. Here, we identify the signaling pathway governing FLP lifetime, which involves integrin-linked kinase (ILK) and ß-parvin, two integrinactin-bridging proteins that block cofilin-mediated actin-filament severing. Notably, the combined actions of Rif/mDia2 and ILK/ß-parvin/cofilin pathways on FLPs are required not only for metastatic outgrowth but also for primary tumor formation following experimental implantation. This provides one mechanistic explanation for how the epithelial-mesenchymal transition (EMT) program imparts tumor-initiating powers to carcinoma cells, since it enhances FLP formation through the activation of ILK/ß-parvin/cofilin pathway.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytoskeleton
/
Actinin
/
Protein Serine-Threonine Kinases
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country: