Non-apoptotic Roles of Caspases in Stem Cell Biology, Carcinogenesis, and Radiotherapy

  • Rayan Kaakati
  • Ruya Zhao
  • Xuhui Bao
  • Andrew K. Lee
  • Xinjian Liu
  • Fang Li
  • Chuan-Yuan LiEmail author
Radiation Biology and Stem Cells (CD Porada and PF Wilson Jr, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Radiation Biology and Stem Cells


Purpose of Review

To summarize recent findings on novel roles of caspases in stem cell biology, tumor repopulation, and tissue regeneration. Contrary to the long-held notion that apoptotic caspases are exclusively executioners of programmed cell death, an abundance of evidence is emerging that activation of caspases does not inevitably lead to cell death.

Recent Findings

It is now known that sublethal activation of caspases occurs in development, stem cell differentiation, epigenetic reprogramming, and a whole host of other key biological processes. Important for cancer biology, recent studies show that activation of caspases in tumors facilitates carcinogenesis, metastasis, and tumor relapse after cancer treatment. We have found that apoptotic cells secrete prostaglandins to stimulate proliferation of neighboring cells. This pathway functions to regenerate tissues and stem cells in multiple organisms, but it also poses problems in emerging tumor resistance to chemotherapy and radiotherapy.


Novel findings on caspases are contrary to established paradigms and might explain why cancer therapies aimed at activating apoptotic caspases have not been very successful in the clinic. In this brief review, we summarize some novel findings regarding caspases with the hope of stimulating more interest in this nascent but increasingly important research area. Better understanding of the diverse roles of caspases may one day help us establish novel approaches for treating cancer.


Stem cell Ionizing radiation Apoptotic caspases Cancer stem cell Carcinogenesis Epigenetic reprogramming 


Funding Information

Work in our laboratory is supported by grants CA208852, CA216876, and ES024015 from the US National Institutes of Health.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

Data described in this study is approved by the Duke University Institutional Animal Care and Use Committee.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Rayan Kaakati
    • 1
  • Ruya Zhao
    • 1
  • Xuhui Bao
    • 2
  • Andrew K. Lee
    • 2
    • 3
  • Xinjian Liu
    • 2
  • Fang Li
    • 2
  • Chuan-Yuan Li
    • 2
    • 3
    Email author
  1. 1.Duke University School of MedicineDurhamUSA
  2. 2.Department of DermatologyDuke University Medical CenterDurhamUSA
  3. 3.Department of Pharmacology and Cancer BiologyDuke University Medical CenterDurhamUSA

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