title: Restoration of ASC expression sensitizes colorectal cancer cells to genotoxic stress-induced caspase-independent cell death.
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.
authors: Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors: Sujeong
authors: S
authors: Hong
authors: Inhwa
authors: I
authors: Hwang
authors: Yun-Sun
authors: YS
authors: Lee
authors: Sangjun
authors: S
authors: Park
authors: Won-Keun
authors: WK
authors: Lee
authors: Teresa
authors: T
authors: Fernandes-Alnemri
authors: Emad S
authors: ES
authors: Alnemri
authors: You-Sun
authors: YS
authors: Kim
authors: Je-Wook
authors: JW
authors: Yu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D053468:CARD Signaling Adaptor Proteins; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019175:DNA Methylation; D017931:DNA Primers; D005047:Etoposide / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D058847:Inflammasomes; D009153:Mutagens; C402202:PYCARD protein, human; D017382:Reactive Oxygen Species; D005047:Etoposide; D020169:Caspases