학술논문
Novel roles of apoptotic caspases in tumor repopulation, epigenetic reprogramming, carcinogenesis, and beyond
Article
Article
Document Type
Academic Journal
Source
Cancer and Metastasis Reviews. September 2018, Vol. 37 Issue 2-3, p227, 10 p.
Subject
Language
English
ISSN
0167-7659
Abstract
Author(s): Ruya Zhao [sup.1], Rayan Kaakati [sup.1], Andrew K. Lee [sup.1] [sup.2], Xinjian Liu [sup.3], Fang Li [sup.3], Chuan-Yuan Li [sup.1] [sup.2] [sup.3] Author Affiliations: (1) 0000 0004 1936 7961, [...]
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.
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.