SDF-1 Chemokine Signalling Modulates the Apoptotic Responses to Iron Deprivation of Clathrin-Depleted DT40 Cells

Alena Pance, Frank R Morrissey-Wettey, Helen Craig, Alison Downing, Richard Talbot, Antony P Jackson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

We have previously deleted both endogenous copies of the clathrin heavy-chain gene in the chicken pre B-cell-line DT40 and replaced them with clathrin under the control of a tetracycline-regulatable promoter (Tet-Off). The originally derived cell-line DKO-S underwent apoptosis when clathrin expression was repressed. We have also described a cell-line DKO-R derived from DKO-S cells that was less sensitive to clathrin-depletion. Here we show that the restriction of transferrin uptake, resulting in iron deprivation, is responsible for the lethal consequence of clathrin-depletion. We further show that the DKO-R cells have up-regulated an anti-apoptotic survival pathway based on the chemokine SDF-1 and its receptor CXCR4. Our work clarifies several puzzling features of clathrin-depleted DT40 cells and reveals an example of how SDF-1/CXCR4 signalling can abrogate pro-apoptotic pathways and increase cell survival. We propose that the phenomenon described here has implications for the therapeutic approach to a variety of cancers.

Original languageEnglish
Pages (from-to)e106278
JournalPLoS ONE
Volume9
Issue number8
DOIs
Publication statusPublished - 27 Aug 2014

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