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Novel roles of apoptotic caspases in tumor repopulation, epigenetic reprogramming, carcinogenesis, and beyond

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Abstract

Apoptotic caspases have long been studied for their roles in programmed cell death and tumor suppression. With recent discoveries, however, it is becoming apparent these cell death executioners are involved in additional biological pathways beyond killing cells. In some cases, apoptotic cells secrete growth signals to stimulate proliferation of neighboring cells. This pathway functions to regenerate tissues in multiple organisms, but it also poses problems in tumor resistance to chemo- and radiotherapy. Additionally, it was found that activation of caspases does not irreversibly lead to cell death, contrary to the established paradigm. Sub-lethal activation of caspases is evident in cell differentiation and epigenetic reprogramming. Furthermore, evidence indicates spontaneous, unprovoked activation of caspases in many cancer cells, which plays pivotal roles in maintaining their tumorigenicity and metastasis. These unexpected findings challenge current cancer therapy approaches aimed at activation of the apoptotic pathway. At the same time, the newly discovered functions of caspases suggest new treatment approaches for cancer and other pathological conditions in the future.

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Funding

The study is supported in part by grants ES024015, CA208852, and CA216876 from the US National Institutes of Health (to C-Y. Li).

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Authors and Affiliations

  1. Duke University School of Medicine, Durham, NC, USA

    Ruya Zhao, Rayan Kaakati, Andrew K. Lee & Chuan-Yuan Li

  2. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3135, Med Ctr, Durham, NC, 27710, USA

    Andrew K. Lee & Chuan-Yuan Li

  3. Department of Dermatology, Duke University Medical Center, Box 3135, Med Ctr, Durham, NC, 27710, USA

    **njian Liu, Fang Li & Chuan-Yuan Li

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  1. Ruya Zhao
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Correspondence to Chuan-Yuan Li.

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Zhao, R., Kaakati, R., Lee, A.K. et al. Novel roles of apoptotic caspases in tumor repopulation, epigenetic reprogramming, carcinogenesis, and beyond. Cancer Metastasis Rev 37, 227–236 (2018). https://doi.org/10.1007/s10555-018-9736-y

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