TY - JOUR TI - The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth AU - Xu, Fei-fei AU - Sun, Hui-min AU - Fang, Run-ping AU - Zhang, Lu AU - Shi, Hui AU - Wang, Xue AU - Fu, Xue-li AU - Li, Xian-meng AU - Shi, Xu-he AU - Wu, Yue AU - Ye, Kai AU - Zhang, Wei-ying AU - Ye, Li-hong T2 - Acta Pharmacologica Sinica AB - 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. DA - 2021/04/06/ PY - 2021 DO - 10.1038/s41401-021-00631-6 DP - www.nature.com SP - 1 EP - 17 LA - en SN - 1745-7254 UR - https://www.nature.com/articles/s41401-021-00631-6 Y2 - 2021/04/08/00:00:54 ER -