Oxidative Stress in Cells with Extra Centrosomes Drives Non-Cell-Autonomous Invasion
- Dev Cell. 2018 Nov 19;47(4):409-424.e9. doi: 10.1016/j.devcel.2018.10.026.
- 1. Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
- 2. Tumour Host Interaction Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK.
- 3. Integrative Cell Signalling and Proteomics, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
- 4. Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Electronic address: [email protected].
Centrosomal abnormalities, in particular centrosome amplification, are recurrent features of human tumors. Enforced centrosome amplification in vivo plays a role in tumor initiation and progression. However, centrosome amplification occurs only in a subset of Cancer cells, and thus, partly due to this heterogeneity, the contribution of centrosome amplification to tumors is unknown. Here, we show that supernumerary centrosomes induce a paracrine-signaling axis via the secretion of proteins, including interleukin-8 (IL-8), which leads to non-cell-autonomous invasion in 3D mammary organoids and zebrafish models. This extra centrosomes-associated secretory phenotype (ECASP) promotes invasion of human mammary cells via HER2 signaling activation. Further, we demonstrate that centrosome amplification induces an early oxidative stress response via increased NOX-generated Reactive Oxygen Species (ROS), which in turn mediates secretion of pro-invasive factors. The discovery that cells with extra centrosomes can manipulate the surrounding cells highlights unexpected and far-reaching consequences of these abnormalities in Cancer.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: CXCR