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HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells

Authors
 Je-Jung Lee  ;  In Ho Park  ;  Man Sup Kwak  ;  Woo Joong Rhee  ;  Songhee H Kim  ;  Jeon-Soo Shin 
Citation
 CELL DEATH DISCOVERY, Vol.7(1) : 28, 2021-02 
Journal Title
CELL DEATH DISCOVERY
Issue Date
2021-02
Abstract
Although cellular senescence has emerged as a novel therapeutic concept in cancer, its underlying mechanisms remain unclear. High mobility group box 1 (HMGB1) and stimulator of interferon genes (STING) are involved in senescence. However, their interactions in senescence have not been reported. Therefore, in this study, we investigated the relationships between HMGB1 and STING in senescence in cancer and other cells. In mouse melanoma cells and several other cell lines, doxorubicin treatment induced senescence in an HMGB1-dependent manner. These responses were mediated by STING, and this function of STING was negatively regulated by the E3 ligase tripartite motif protein 30α (TRIM30α). We also found that HMGB1 bound to the TRIM30α promoter and then suppressed its expression by inhibiting its transcription, which enhanced STING-induced senescence. This mechanism was further mediated by signal transducer and activator of transcription 6 (STAT6) and p21. Overall, our findings demonstrated that HMGB1 orchestrated STING-STAT6-p21-mediated senescence by regulating TRIM30α as an alternative anticancer mechanism.
Files in This Item:
T202102279.pdf Download
DOI
10.1038/s41420-021-00409-z
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Man Sup(곽만섭) ORCID logo https://orcid.org/0000-0002-3989-3016
Kim, Sung-Hee(김성희)
Park, Inho(박인호) ORCID logo https://orcid.org/0000-0003-2190-5469
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Rhee, Woo Joong(이우중) ORCID logo https://orcid.org/0000-0001-9690-0553
Lee, Je-Jung(이제정)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184133
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