RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27071537.
- Also identified by DOI 10.1038/ncomms11245 and PMC identifier 4833863.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
RAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct RAS binding to PI3-Kinase in this remains uncertain. Here, we provide evidence that disruption of RAS interaction with PI3-Kinase p110α decreases cell motility and prevents activation of Rac GTPase. Analysis of gene expression in cells lacking RAS interaction with p110α reveals increased levels of the extracellular matrix glycoprotein Reelin and activation of its downstream pathway resulting in upregulation of E-cadherin expression. Induction of the Reelin/E-cadherin axis is also observed in Kras mutant lung tumours that are regressing due to blockade of RAS interaction with PI3-Kinase. Furthermore, loss of Reelin correlates with decreased survival of lung and breast cancer patients. Reelin thus plays a role in restraining RAS and PI3-kinase promotion of cell motility and potentially tumour metastasis.
Medical subject headings
- Cell Adhesion Molecules, Neuronal
- Cell Movement
- Extracellular Matrix Proteins
- Nerve Tissue Proteins
- Phosphatidylinositol 3-Kinases
- Serine Endopeptidases
- Signal Transduction
- ras Proteins