Two Sides of the Same Coin – Compensatory Proliferation in Regeneration and Cancer

  • Neha Diwanji
  • Andreas BergmannEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1167)


Apoptosis has long been regarded as a tumor suppressor mechanism and evasion from apoptosis is considered to be one hallmark of cancer. However, this principle is not always consistent with clinical data which often illustrate a correlation between apoptosis and poor prognosis. Work in the last 15 years has provided an explanation for this apparent paradox. Apoptotic cells communicate with their environment and can produce signals which promote compensatory proliferation of surviving cells. This behavior of apoptotic cells is important for tissue regeneration in several model organisms, ranging from hydra to mammals. However, it may also play an important feature for tumorigenesis and tumor relapse. Several distinct forms of apoptosis-induced compensatory proliferation (AiP) have been identified, many of which involve reactive oxygen species (ROS) and immune cells. One type of AiP, “undead” AiP, in which apoptotic cells are kept in an immortalized state and continuously divide, may have particular relevance for tumorigenesis. Furthermore, given that chemo- and radiotherapy often aim to kill tumor cells, an improved understanding of the effects of apoptotic cells on the tumor and the tumor environment is of critical importance for the well-being of the patient. In this review, we summarize the current knowledge of AiP and focus our attention on recent findings obtained in Drosophila and other model organisms, and relate them to tumorigenesis.


Apoptosis-induced proliferation Caspases Reactive oxygen species Macrophages Drosophila 



This work was supported by the National Institute of General Medical Sciences (NIGMS) under award number R35GM118330. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Molecular, Cell and Cancer BiologyUniversity of Massachusetts Medical SchoolWorcesterUSA

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