RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression.
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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.
rac1 GTP-Binding Protein
Cell Adhesion Molecules, Neuronal
Nerve Tissue Proteins
Extracellular Matrix Proteins
Lung Cancer Group
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Nature communications, 2016, 7 pp. 11245 - ?
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0
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