PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

Yamu Li; Zhonghua Liu; Yiqing Zhao; Jie Yang; Tsan Sam Xiao; Ronald A. Conlon; Zhenghe Wang

doi:10.1016/j.gendis.2022.11.003

您当前的位置：

首页 >

文章列表页 >

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

Full-length article | 更新时间：2023-08-29

- PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain
- PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain
- Genes & Diseases 2023年10卷第4期
- 作者机构：
  
  1. Department of Pathology, Case Western Reserve University,OH,Cleveland,USA,44106
  2. Department of Genetics and Genome Sciences, Case Western Reserve University,OH,Cleveland,USA,44106
  3. Department of Physiology and Biophysics, Case Western Reserve University,OH,Cleveland,USA,44106
  4. Case Comprehensive Cancer Center, Case Western Reserve University,OH,Cleveland,USA,44106
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.11.003
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-7-1，
扫描看全文
Yamu Li, Zhonghua Liu, Yiqing Zhao, 等. PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain[J]. Genes & Diseases, 2023,10(4).

Yamu Li, Zhonghua Liu, Yiqing Zhao, et al. PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain[J]. Genes & Diseases, 2023,10(4).
Yamu Li, Zhonghua Liu, Yiqing Zhao, 等. PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain[J]. Genes & Diseases, 2023,10(4). DOI： 10.1016/j.gendis.2022.11.003.

Yamu Li, Zhonghua Liu, Yiqing Zhao, et al. PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain[J]. Genes & Diseases, 2023,10(4). DOI： 10.1016/j.gendis.2022.11.003.

摘要

Abstract

How PD-L1 expression is regulated in cancer is poorly understood. Here

we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers (CRCs). ERBB3 is one of the four members of the EGF receptor family

all with protein tyrosine kinase domains. ERBB3 is a pseudokinase with a high binding affinity to ATP. We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines. The ERBB3 ATP-binding mutant cells dramatically reduce IFN-γ-induced PD-L1 expression. Mechanistically

ERBB3 regulates IFN-γ-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells. Knockin of a tumor-derived ERBB3 mutation located in the kinase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy

suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune checkpoint therapy.

关键词

Keywords

Colon cancerERBB3ImmunotherapyPD-L1Pseudokinase

references

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy

Cancer organoids: A platform in basic and translational research

Targeting CD47-SIRPα axis for Hodgkin and non-Hodgkin lymphoma immunotherapy

The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients