Apoptosis-induced FGF signalling promotes non-cell autonomous resistance to cell death

Abstract

AbstractDamaged or superfluous cells are often eliminated by apoptosis. Although a cell-autonomous process, apoptotic cells communicate with their environment in different ways. However, the extent to which apoptotic cells alerting their neighbours to potential danger is unclear. Addressing this question, here we describe a mechanism whereby dying cells can promote survival of neighbouring cells. We find that during apoptosis, 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 prosurvival BCL-2 proteins in turn can protect neighbouring cells from apoptosis. Accordingly, we find in certain cancer types a correlation between FGF-signalling, BCL-2 expression and worse prognosis. Importantly, either co-treatment with FGF-receptor inhibitors or removal of apoptotic stress restores apoptotic sensitivity. These data reveal a pathway by which dying cells can increase resistance to cell death in surrounding cells. Beyond mediating cytotoxic drug resistance, this process may serve additional roles, for instance limiting tissue damage in response to stress.