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DGG-100629 inhibits lung cancer growth by suppressing the NFATc1/DDIAS/STAT3 pathway

Authors
 Joo-Young Im  ;  Bo-Kyung Kim  ;  Sung-Hoon Yoon  ;  Byoung Chul Cho  ;  Yu Mi Baek  ;  Mi-Jung Kang  ;  Nayeon Kim  ;  Young-Dae Gong  ;  Misun Won 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.53(4) : 643-653, 2021-04 
Journal Title
EXPERIMENTAL AND MOLECULAR MEDICINE
ISSN
 1226-3613 
Issue Date
2021-04
Abstract
DNA damage-induced apoptosis suppressor (DDIAS) promotes the progression of lung cancer and hepatocellular carcinoma through the regulation of multiple pathways. We screened a chemical library for anticancer agent(s) capable of inhibiting DDIAS transcription. DGG-100629 was found to suppress lung cancer cell growth through the inhibition of DDIAS expression. DGG-100629 induced c-Jun NH(2)-terminal kinase (JNK) activation and inhibited NFATc1 nuclear translocation. Treatment with SP600125 (a JNK inhibitor) or knockdown of JNK1 restored DDIAS expression and reversed DGG-100629-induced cell death. In addition, DGG-100629 suppressed the signal transducer and activator of transcription (STAT3) signaling pathway. DDIAS or STAT3 overexpression restored lung cancer cell growth in the presence of DGG-100629. In a xenograft assay, DGG-100629 inhibited tumor growth by reducing the level of phosphorylated STAT3 and the expression of STAT3 target genes. Moreover, DGG-100629 inhibited the growth of lung cancer patient-derived gefitinib-resistant cells expressing NFATc1 and DDIAS. Our findings emphasize the potential of DDIAS blockade as a therapeutic approach and suggest a novel strategy for the treatment of gefitinib-resistant lung cancer.
Files in This Item:
T202103936.pdf Download
DOI
10.1038/s12276-021-00601-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184886
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