The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth
© 2021. The Author(s), under exclusive licence to CPS and SIMM..
Programmed death ligand-1 (PD-L1)/PD-1 checkpoint extensively serves as a central mediator of immunosuppression. A tumor-promoting role for abundant PD-L1 in several cancers is revealed. However, the importance of PD-L1 and how the PD-L1 expression is controlled in breast cancer remains obscure. Here, the mechanisms of controlling PD-L1 at the transcription and protein acetylation levels in promoting breast cancer growth are presented. Overexpressed PD-L1 accelerates breast cancer growth in vitro and in vivo. RNA-seq uncovers that PD-L1 can induce some target genes affecting many cellular processes, especially cancer development. In clinical breast cancer tissues and cells, PD-L1 and HBXIP are both increased, and their expressions are positively correlated. Mechanistic exploration identifies that HBXIP stimulates the transcription of PD-L1 through co-activating ETS2. Specifically, HBXIP induces PD-L1 acetylation at K270 site through interacting with acetyltransferase p300, leading to the stability of PD-L1 protein. Functionally, depletion of HBXIP attenuates PD-L1-accelerated breast tumor growth. Aspirin alleviates breast cancer via targeting PD-L1 and HBXIP. Collectively, the findings display new light into the mechanisms of controlling tumor PD-L1 and broaden the utility for PD-L1 as a target in breast cancer therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Acta pharmacologica Sinica - 43(2022), 2 vom: 06. Feb., Seite 429-445 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Fei-Fei [VerfasserIn] |
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| Links: |
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| Themen: |
Adaptor Proteins, Signal Transducing |
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| Anmerkungen: |
Date Completed 16.03.2022 Date Revised 02.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41401-021-00631-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Programmed death ligand-1 (PD-L1)/PD-1 checkpoint extensively serves as a central mediator of immunosuppression. A tumor-promoting role for abundant PD-L1 in several cancers is revealed. However, the importance of PD-L1 and how the PD-L1 expression is controlled in breast cancer remains obscure. Here, the mechanisms of controlling PD-L1 at the transcription and protein acetylation levels in promoting breast cancer growth are presented. Overexpressed PD-L1 accelerates breast cancer growth in vitro and in vivo. RNA-seq uncovers that PD-L1 can induce some target genes affecting many cellular processes, especially cancer development. In clinical breast cancer tissues and cells, PD-L1 and HBXIP are both increased, and their expressions are positively correlated. Mechanistic exploration identifies that HBXIP stimulates the transcription of PD-L1 through co-activating ETS2. Specifically, HBXIP induces PD-L1 acetylation at K270 site through interacting with acetyltransferase p300, leading to the stability of PD-L1 protein. Functionally, depletion of HBXIP attenuates PD-L1-accelerated breast tumor growth. Aspirin alleviates breast cancer via targeting PD-L1 and HBXIP. Collectively, the findings display new light into the mechanisms of controlling tumor PD-L1 and broaden the utility for PD-L1 as a target in breast cancer therapy | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PD-L1 | |
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| 700 | 1 | |a Zhang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xue |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Xue-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xian-Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xu-He |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Li-Hong |e verfasserin |4 aut | |
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