@article{8c3bab6e4aec44568409050be8dbe715,
title = "Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death",
abstract = "Damaged or superfluous cells are typically eliminated by apoptosis. Although apoptosis is a cell-autonomous process, apoptotic cells communicate with their environment in different ways. Here we describe a mechanism whereby cells under apoptotic stress can promote survival of neighbouring cells. We find that upon apoptotic stress, cells release the growth factor FGF2, leading to MEK-ERK-dependent transcriptional upregulation of pro-survival BCL-2 proteins in a non-cell autonomous manner. This transient upregulation of pro-survival BCL-2 proteins protects neighbouring cells from apoptosis. Accordingly, we find in certain cancer types a correlation between FGF-signalling, BCL-2 expression and worse prognosis. In vivo, upregulation of MCL-1 occurs in an FGF-dependent manner during skin repair, which regulates healing dynamics. Importantly, either co-treatment with FGF-receptor inhibitors or removal of apoptotic stress restores apoptotic sensitivity to cytotoxic therapy and delays wound healing. These data reveal a pathway by which cells under apoptotic stress can increase resistance to cell death in surrounding cells. Beyond mediating cytotoxic drug resistance, this process also provides a potential link between tissue damage and repair.Apoptosis is a cellular process that eliminates damaged or superfluous cells. Here the authors show that cells undergoing apoptotic stresss secrete the growth factor FGF2, which upregulates pro-survival BCL-2 proteins in neighbouring cells, thereby promoting their survival.",
keywords = "FIBROBLAST-GROWTH-FACTOR, STEM-CELLS, MEMBRANE PERMEABILIZATION, ANTITUMOR-ACTIVITY, GENE-PRODUCT, KINASE, INHIBITOR, BCL-2, EXPRESSION, SURVIVAL",
author = "F.J. Bock and E. Sedov and E. Koren and A.L. Koessinger and C. Cloix and D. Zerbst and D. Athineos and J. Anand and K.J. Campbell and K. Blyth and Y. Fuchs and S.W.G. Tait",
note = "Funding Information: This work was supported by Cancer Research UK grant C40872/A2014 (S.W.G.T), CRUK core funding A29799 to K.B. and a Tenovus small pilot grant (F.J.B). We thank Joel Riley and Catherine Winchester for reviewing the manuscript and all members of the Tait laboratory for helpful suggestions as well as Hasan Uludağ (University of Alberta, Canada) for reagents. We would like to thank the Core Services and Advanced Technologies at the Cancer Research UK Beatson Institute (C596/A17196), with particular thanks to the Beatson Advanced Imaging Resource, Biological Services Unit, Histology and Molecular Technologies. Schematic figures were created using BioRender.com. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = nov,
day = "12",
doi = "10.1038/s41467-021-26613-0",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}