Research ArticleCell Biology

Short-term cellular memory tunes the signaling responses of the chemokine receptor CXCR4

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Science Signaling  09 Jul 2019:
Vol. 12, Issue 589, eaaw4204
DOI: 10.1126/scisignal.aaw4204

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Remembering the past for CXCR4 signaling

Activation of the chemokine receptor CXCR4 by its ligand CXCL12 enables cancer cells to disseminate and metastasize. Spinosa et al. performed imaging analysis and computational modeling to analyze signaling responses mediated by CXCR4 at the single-cell level. CXCR4 can signal through the kinases Akt and ERK. The authors found that exposing cells to different growth-promoting stimuli before CXCL12 altered the activity of upstream kinases (PI3K and Ras) or of a common downstream kinase complex (mTORC1) to bias CXCR4 signaling through either Akt or ERK. Furthermore, kinase inhibitors that are clinically used to treat cancer increased the likelihood of CXCR4 activation of Akt and/or ERK, suggesting that such drugs may inadvertently promote pro-metastatic CXCR4 signaling.