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.

Fei-fei Xu;Hui-min Sun;Run-ping Fang;Lu Zhang;Hui Shi;Xue Wang;Xue-li Fu;Xian-meng Li;Xu-he Shi;Yue Wu;Kai Ye;Wei-ying Zhang;Li-hong Ye

State Key Laboratory of Medicinal Chemical Biology,Tianjin Key Laboratory of Protein Sciences,Department of Biochemistry,College of Life Sciences,Nankai University,Tianjin 300071,China

中国药理学报（英文版）

[1]Fei-fei Xu;Hui-min Sun;Run-ping Fang;Lu Zhang;Hui Shi;Xue Wang;Xue-li Fu;Xian-meng Li;Xu-he Shi;Yue Wu;Kai Ye;Wei-ying Zhang;Li-hong Ye-.The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth)[J].中国药理学报（英文版）,2022(02):429-445

HBXIP,Overexpressed,ETS2

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