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  2. The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth

The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth

  • Acta Pharmacol Sin. 2022 Feb;43(2):429-445. doi: 10.1038/s41401-021-00631-6.
Fei-Fei Xu 1 Hui-Min Sun 1 Run-Ping Fang 1 Lu Zhang 1 Hui Shi 1 Xue Wang 1 Xue-Li Fu 1 Xian-Meng Li 1 Xu-He Shi 1 Yue Wu 1 Kai Ye 1 Wei-Ying Zhang 2 Li-Hong Ye 3
Affiliations

Affiliations

  • 1 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.
  • 2 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. [email protected].
  • 3 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. [email protected].
Abstract

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.

Keywords

HBXIP; PD-L1; breast cancer; protein acetylation; transcription activation.

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