Cited 7 times in
STING mediates nuclear PD-L1 targeting-induced senescence in cancer cells
DC Field | Value | Language |
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dc.contributor.author | 신전수 | - |
dc.contributor.author | 이제정 | - |
dc.date.accessioned | 2022-12-22T03:37:26Z | - |
dc.date.available | 2022-12-22T03:37:26Z | - |
dc.date.issued | 2022-09 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/191921 | - |
dc.description.abstract | Immune checkpoint molecule programmed death-ligand 1 (PD-L1) is overexpressed in cancer cells and imparts resistance to cancer therapy. Although membrane PD-L1 has been targeted for cancer immune therapy, nuclear PD-L1 was reported to confer cancer resistance. Therefore, it is important to regulate the nuclear PD-L1. The mechanisms underlying the therapeutic efficacy of PD-L1 targeting have not been well-established. Cellular senescence has been considered a pivotal mechanism to prevent cancer progression, and recently, PD-L1 inhibition was shown to be involved in cancer cell senescence. However, the relevance of PD-L1 targeting-induced senescence and the role of stimulator of interferon genes (STING) has not been reported. Therefore, we aimed to identify the role of PD-L1 in cancer progression and how it regulates cancer prevention. In this study, we found that PD-L1 depletion-induced senescence via strong induction of STING expression in mouse melanoma B16-F10 and colon cancer CT26 cells, and in human melanoma A375 and lung cancer A549 cells. Interestingly, nuclear PD-L1 silencing increased STING promoter activity, implying that PD-L1 negatively regulates STING expression via transcriptional modulation. Furthermore, we showed that PD-L1 binds to the STING promoter region, indicating that PD-L1 directly controls STING expression to promote cancer growth. In addition, when we combined PD-L1 silencing with the senescence-inducing chemotherapeutic agent doxorubicin, the effect of PD-L1-targeting was even more powerful. Overall, our findings can contribute to the understanding of the role of PD-L1 in cancer therapy by elucidating a novel mechanism for PD-L1 targeting in cancer cells. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | CELL DEATH & DISEASE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | B7-H1 Antigen* / metabolism | - |
dc.subject.MESH | Doxorubicin | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immune Checkpoint Proteins | - |
dc.subject.MESH | Interferons | - |
dc.subject.MESH | Melanoma* / metabolism | - |
dc.subject.MESH | Membrane Proteins / metabolism* | - |
dc.subject.MESH | Mice | - |
dc.title | STING mediates nuclear PD-L1 targeting-induced senescence in cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Microbiology (미생물학교실) | - |
dc.contributor.googleauthor | Je-Jung Lee | - |
dc.contributor.googleauthor | So Young Kim | - |
dc.contributor.googleauthor | Songhee H Kim | - |
dc.contributor.googleauthor | Seoyeon Choi | - |
dc.contributor.googleauthor | Bin Lee | - |
dc.contributor.googleauthor | Jeon-Soo Shin | - |
dc.identifier.doi | 10.1038/s41419-022-05217-6 | - |
dc.contributor.localId | A02144 | - |
dc.relation.journalcode | J00482 | - |
dc.identifier.eissn | 2041-4889 | - |
dc.identifier.pmid | 36109513 | - |
dc.contributor.alternativeName | Shin, Jeon Soo | - |
dc.contributor.affiliatedAuthor | 신전수 | - |
dc.citation.volume | 13 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 791 | - |
dc.identifier.bibliographicCitation | CELL DEATH & DISEASE, Vol.13(9) : 791, 2022-09 | - |
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