AI Article Synopsis
- * The study identifies that the RAPGEF2 protein is quickly phosphorylated and degraded when exposed to factors that stimulate cell movement, influencing how cells migrate.
- * Blocking the degradation of RAPGEF2 leads to increased Rap1 activity and reduced migration in response to a strong cancer-promoting factor, suggesting a critical link between IKKβ and cell movement in relation to cancer metastasis.
Article Abstract
Epithelial cell migration is crucial for the development and regeneration of epithelial tissues. Aberrant regulation of epithelial cell migration has a major role in pathological processes such as the development of cancer metastasis and tissue fibrosis. Here, we report that in response to factors that promote cell motility, the Rap guanine exchange factor RAPGEF2 is rapidly phosphorylated by I-kappa-B-kinase-β and casein kinase-1α and consequently degraded by the proteasome via the SCF(βTrCP) ubiquitin ligase. Failure to degrade RAPGEF2 in epithelial cells results in sustained activity of Rap1 and inhibition of cell migration induced by HGF, a potent metastatic factor. Furthermore, expression of a degradation-resistant RAPGEF2 mutant greatly suppresses dissemination and metastasis of human breast cancer cells. These findings reveal a molecular mechanism regulating migration and invasion of epithelial cells and establish a key direct link between IKKβ and cell motility controlled by Rap-integrin signaling.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.devcel.2013.10.023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!