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Restoration of ASC expression sensitizes colorectal cancer cells to genotoxic stress-induced caspase-independent cell death

Authors
 Sujeong Hong ; Inhwa Hwang ; Je-Wook Yu ; You-Sun Kim ; Emad S. Alnemri ; Teresa Fernandes-Alnemri ; Won-Keun Lee ; Sangjun Park ; Yun-Sun Lee 
Citation
 Cancer Letters, Vol.331(2) : 183~191, 2013 
Journal Title
 Cancer Letters 
ISSN
 0304-3835 
Issue Date
2013
Abstract
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), an essential component of the inflammasome complex, is frequently silenced by epigenetic methylation in many tumor cells. Here, we demonstrate that restoration of ASC expression in human colorectal cancer DLD-1 cells, in which ASC is silenced by aberrant methylation, potentiated cell death mediated by DNA damaging agent. Contrarily, ASC knockdown in HT-29 cells rendered cells less susceptible to etoposide toxicity. The increased susceptibility of ASC-expressing DLD-1 cells to genotoxic stress was independent of inflammasome or caspase activation, but partially dependent on mitochondrial ROS production and JNK activation. Thus, our data suggest that ASC expression in cancer cells is an important factor in determining their susceptibility to chemotherapy.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86421
DOI
10.1016/j.canlet.2012.12.020
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
Yonsei Authors
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