Journal Article

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

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

2022

Overview

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.

• Publisher: Springer Singapore,Nature Publishing Group
• Subject: Acetylation / Acetyltransferase / Adaptor Proteins, Signal Transducing - metabolism / Animals / Apoptosis / Aspirin / B7-H1 Antigen - metabolism / Biomedical and Life Sciences / Biomedicine / Blotting, Western / Breast cancer / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cell Line, Tumor / Cell Proliferation / Chromatin Immunoprecipitation / Ets-2 protein / Female / Fluorescent Antibody Technique / Humans / Immunology / Immunosuppression / Internal Medicine / L1 protein / MCF-7 Cells / Medical Microbiology / Mice / Mice, Nude / Neoplasm Transplantation / PD-1 protein / PD-L1 protein / Pharmacology/Toxicology / Real-Time Polymerase Chain Reaction / Reverse Transcriptase Polymerase Chain Reaction / Transcription / Tumors / Vaccine