10779/rcsi.10791395.v1 Karen Boland Karen Boland Lorna Flanagan Lorna Flanagan Jochen HM Prehn Jochen HM Prehn Paracrine control of tissue regeneration and cell proliferation by Caspase-3. Royal College of Surgeons in Ireland 2019 Caspases Apoptosis Cell Proliferation Regeneration Stem Cells Cancer Physiology Medical Physics 2019-11-22 16:58:43 Journal contribution https://repository.rcsi.com/articles/journal_contribution/Paracrine_control_of_tissue_regeneration_and_cell_proliferation_by_Caspase-3_/10791395 <p>Executioner caspases such as Caspase-3 and Caspase-7 have long been recognised as the key proteases involved in cell demolition during apoptosis. Caspase activation also modulates signal transduction inside cells, through activation or inactivation of kinases, phosphatases and other signalling molecules. Interestingly, a series of recent studies have demonstrated that caspase activation may also influence signal transduction and gene expression changes in neighbouring cells that themselves did not activate caspases. This review describes the physiological relevance of paracrine Caspase-3 signalling for developmental processes, tissue homeostasis and tissue regeneration, and discusses the role of soluble factors and microparticles in mediating these paracrine activities. While non-cell autonomous control of tissue regeneration by Caspase-3 may represent an important process for maintaining tissue homeostasis, it may limit the efficiency of current cancer therapy by promoting cell proliferation in those cancer cells resistant to radio- or chemotherapy. We discuss recent evidence in support of such a role for Caspase-3, and discuss its therapeutic implication.</p>