Edinburgh Research Explorer

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

Research output: Contribution to journalArticle

Related Edinburgh Organisations

Open Access permissions

Open

Documents

  • Download as Adobe PDF

    Rights statement: Copyright: © 2014 Pance et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Final published version, 1 MB, PDF document

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0106278
Original languageEnglish
Pages (from-to)e106278
JournalPLoS ONE
Volume9
Issue number8
DOIs
Publication statusPublished - 27 Aug 2014

Abstract

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.

Download statistics

No data available

ID: 16882030