During apoptosis-induced proliferation (AiP), dying cells secrete mitogenic signals, inducing proliferation of the surviving cells to compensate for the tissue loss. Apoptosis-induced proliferation is a normal response to injury or stress-induced cell death, however, AiP can also contribute to initial tumor growth and to tumor repopulation following radiation or chemotherapy.
Contributions from Drosophila research have played a major role in elucidating the processes and players involved in apoptosis (see, for example, Fuchs and Steller, 2011, FBrf0240836). More recently, the process of apoptosis-induced proliferation has been studied in the fly, including the role of caspases (for example, Dmel\Dronc) and reactive oxygen species (ROS) (induced, for example, using Dmel\Duox). A fly model of apoptosis, described as the "undead" model, combines expression of an apoptotic signaling gene with (such as hid or rpr) with BacA\p35, which blocks cell death; this results in a prolonged AiP state.
In fly models of epithelial hyperplastic proliferation, hemocytes (analogous to vertebrate macrophages) appear to be recruited in the process of AiP and are thought to contribute to proliferative signaling via the tumor necrosis factor (TNF) ortholog Dmel\egr.
Caspases may also impact the initiation and progression of cancer via other regulatory processes; see Xu et al., 2018 (FBrf0239040).
[updated Oct. 2019 by FlyBase; FBrf0222196]
Apoptosis-induced proliferation (AiP) maintains tissue homeostasis following massive stress-induced cell death. During this process dying cells secrete mitogenic signals, inducing proliferation of the surviving cells to compensate for the tissue loss. In addition to wound healing and tissue regeneration, AiP contributes to tumor repopulation following radiation or chemotherapy. [Diwanji and Bergmann, 2018, FBrf0239212; Diwanji and Bergmann, 2017, FBrf0234662]
See also Labi and Erlacher, 2015; pubmed:25741600.
Active caspases are the main inducers of AiP. Caspases are conserved cysteine proteases present in cells as inactive zymogens. After apoptosis induction, caspases are activated in a sequential cascade that culminates in the death of the cell. During AiP, before they die, apoptotic cells emit signals to neighboring surviving cells to promote compensatory proliferation and maintain tissue homeostasis.
Sole TNF family gene in Drosophila (1 Drosophila to many human); Dmel\egr is most closely related to human EDA, TNFSF13, and TNFSF13B.
Low-scoring ortholog of human CASP2, CASP14, abd CASP1 (1 Drosophila to 3 human); multiple other homologous genes in both species. Dmel\Dronc shares 20-26% identity and 40-41% similarity with the human genes.
High-scoring ortholog of human DUOX1 and DUOX2; multiple additional low-scoring genes in human (1 Drosophila to many human). Dmel\Duox shares 39-40% identity and 57% similarity with DUOX1 and DUOX2.
