Targeting lectin-like oxidized low-density lipoprotein receptor-1 triggers autophagic program in esophageal cancer

  • Cell Death Differ. 2022 Apr;29(4):697-708. doi: 10.1038/s41418-021-00884-y.
Can Li   #  1 ,  Fenglin Liu   #  2 ,  Xu Yang   #  1 ,  Bao Guo  1 ,  Guoyun Li  3 ,  Jie Yin  2 ,  Gaofei He  1 ,  Caiting Yang  4 ,  Ling Xu  1 ,  Shuxuan Li  1 ,  Hao Wu  1 ,  Hai Liu  4 ,  Yuanyuan Ruan  1 ,  Jianxin Gu  1 ,  Lan Wang  5
Affiliations
  • 1. NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 2. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 20032, China.
  • 3. Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, China.
  • 4. Institutes of Biomedical Sciences, Shanxi University, Taiyuan, 030006, China.
  • 5. NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. [email protected].
  • # Contributed equally.
PMID: 34611296 DOI: 10.1038/s41418-021-00884-y
Abstract

Autophagy is a highly conserved catabolic process to maintain cellular homeostasis. However, dysfunctional Autophagy contributes to a context-dependent role in Cancer. Here, we clarified the exact role of Autophagy modulated by the scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in Esophageal Cancer (EC). A comprehensive analysis in various cancers displayed that LOX-1 was upregulated the most in EC tissues and associated with poor prognosis of patients. Deletion of LOX-1 ex vivo and in vivo suppresses EC development by inducing autophagic cell death. Receptor for activated C kinase 1 (RACK1) was identified as a signal adapter of LOX-1, which incented Ras/MEK/ERK pathway and TFEB nuclear export signal and safeguarded tumorigenesis. A sulfated polysaccharide fucoidan extracted from Brown seaweed was found to bind with LOX-1 and mediate its proteasomal degradation but not the lysosome pathway, leading to autophagy-related cell death in EC. These results reveal a central contribution of LOX-1 to EC development and provide genetic ablation or bioactive polysaccharide as an effective intervention for EC therapy.

Products