Data from Asialoglycoprotein Receptor 1 Functions as a Tumor Suppressor in Liver Cancer via Inhibition of STAT3

• DOI: 10.1158/0008-5472.c.6514125
• Publication Date: 2024-03-12T22:46:19Z
• Authors: Xingxin Zhu; Guangyuan Song; Shiyu Zhang; Jun Chen; Xiaoyi Hu; Hai Zhu; Xing Jia; Zequn Li; Wenfeng Song; Jian Chen; Cheng Jin; Mengqiao Zhou; Yongchao Zhao; Haiyang Xie; Shusen Zheng; Penghong Song
• Keywords: Asialoglycoprotein receptor; Liver Cancer

<div>Abstract<p>Liver cancer is characterized by aggressive growth and high mortality. Asialoglycoprotein receptor 1 (ASGR1), which expressed almost exclusively in liver cells, reduced cancer. However, the specific mechanism of ASGR1 function has not been fully elucidated. On basis database screening, we identified as a tumor suppressor regulated DNA methylation. Expression was downregulated correlated with size, grade, survival. Functional gain loss experiments showed that suppresses progression <i>in vivo</i> vitro</i>. RNA sequencing mass spectrometry inhibits tyrosine phosphorylation STAT3 interacting Nemo-like kinase (NLK). NLK bound SH2 domain an ATP-dependent manner competed glycoprotein 130 (GP130), ultimately suppressing GP130/JAK1-mediated STAT3. altered binding strength GP130. Furthermore, region crucial for curbing its phosphorylation. Collectively, these results confirm promoting to inhibiting phosphorylation, suggesting approaches activate ASGR1–NLK axis may be potential therapeutic strategy this disease.</p>Significance:<p>ASGR1 downregulation methylation facilitates tumorigenesis increasing phosphorylation.</p></div>