Grp78 is required for intestinal Kras-dependent glycolysis proliferation and adenomagenesis.
Life science alliance(2023)
摘要
In development of colorectal cancer, mutations in are often followed by mutations in oncogene The latter changes cellular metabolism and is associated with the Warburg phenomenon. Glucose-regulated protein 78 () is an important regulator of the protein-folding machinery, involved in processing and localization of transmembrane proteins. We hypothesize that targeting in and ()-mutant intestines interferes with the metabolic phenotype imposed by mutations. In mice with intestinal epithelial mutations in , and heterozygosity for ( ) adenoma number and size is decreased compared with mice. Organoids from mice exhibited a glycolysis metabolism which was completely rescued by heterozygosity. Expression and correct localization of glucose transporter GLUT1 was diminished in cells. GLUT1 inhibition restrained the increased growth observed in -mutant organoids, whereas organoids were unaffected. We identify as a critical factor in mutated adenomagenesis. This can be attributed to a critical role for in GLUT1 expression and localization, targeting glycolysis and the Warburg effect.
更多查看译文
关键词
kras-dependent
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要