Format

Send to

Choose Destination
PLoS Biol. 2013 Jul;11(7):e1001615. doi: 10.1371/journal.pbio.1001615. Epub 2013 Jul 23.

The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

Author information

1
Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas-CSIC-University of Salamanca, Salamanca, Spain.

Abstract

The catalytic activity of GDP/GTP exchange factors (GEFs) is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.

Comment in

PMID:
23935450
PMCID:
PMC3720258
DOI:
10.1371/journal.pbio.1001615
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center