p62-mediated tumor metabolic reprogramming:structural basis,function and signal integration
Yue Yuanyuan
Qu Chongxiao
Shi Xiangcheng
Guo Chenjia
Abstract：As a key multifunctional adaptor protein in cells,sequestosome-1(p62)is not only a substrate receptor in the autophagy pathway,but also a hub connecting signal transduction and metabolic regulation.Although studies have shown that p62 is abnormally highly expressed in various malignant tumors such as hepato-cellular carcinoma,pancreatic cancer,renal cancer and colorectal cancer,the molecular mechanism by which it drives tumor metabolic reprogramming remains incompletely clear.This article systematically reviews the molecular mechanism by which p62 integrates mammalian target of rapamycin complex 1,nuclear factor erythroid 2-related factor 2,and nuclear factor-κB signaling axes through non-canonical autophagy pathways to coordinately regulate the stability of glucose transporters,glycolytic rate-limiting enzymes,and glutamine transporters,thereby remodeling the glycolipid metabolic network of tumor cells.In addition,this article further discusses metabolic intervention therapeutic strategies targeting p62 signaling nodes,providing a theoretical basis for the development of novel combined anti-tumor therapies.
Keywords：Tumor metabolic reprogrammingp62Signaling pathwayTargeted therapy
Publication Date：2026-06-18
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：5( 956-960 )