Apoptosis-induced proliferation (AiP) maintains tissue homeostasis following massive stress-induced cell death. During this phenomenon, dying cells induce proliferation of the surviving cells to compensate for the tissue loss, and thus restore organ size. Along with wound healing and tissue regeneration, AiP also contributes to tumor repopulation following radiation or chemotherapy. There are several models of AiP. Using an “undead” AiP model that causes hyperplastic overgrowth of Drosophila epithelial tissue, we recently demonstrated that extracellular reactive oxygen species (eROS) are produced by undead epithelial cells, and are necessary for inducing AiP and overgrowth. Furthermore, hemocytes, the Drosophila blood cells, are seen adjacent to the undead epithelial tissue, and may secrete the TNF ortholog Eiger that signals through the TNF receptor to active Jun-N-terminal kinase (JNK) in the undead tissue and induce proliferation. We propose that undead epithelial tissue triggers an inflammatory response that resembles recruitment of macrophages to human epithelial tumors, and that these tumor-associated macrophages release signals for proliferation and tumor growth of the epithelium. This Extra View article summarizes these recent findings with a focus on the role of eROS for promoting regeneration and inflammation-induced tumorigenesis.

在大量应激诱导的细胞死亡后，细胞凋亡诱导的增殖（AiP）维持组织稳态。在这种现象期间，垂死的细胞诱导存活细胞的增殖以补偿组织损失，从而恢复器官大小。除了伤口愈合和组织再生外，AiP还有助于放疗或化疗后肿瘤的重新聚集。有几种AiP模型。最近，使用导致果蝇上皮组织增生过度的“不死” AiP模型，我们最近证明了不死上皮细胞会产生细胞外活性氧（eROS），并且是诱导AiP和过度生长的必要条件。此外，血细胞，果蝇血细胞，可见于不死上皮组织附近，并可能分泌TNF直向同源物Eiger，该信号通过TNF受体传递信号至不死组织中的活性Jun-N末端激酶（JNK），并诱导增殖。我们提出不死上皮组织触发类似于巨噬细胞募集到人类上皮肿瘤的炎症反应，并且这些与肿瘤相关的巨噬细胞释放上皮的增殖和肿瘤生长的信号。这篇Extra View文章总结了这些最新发现，重点是eROS在促进再生和炎症诱导的肿瘤发生中的作用。