KHK-A promotes fructose-dependent colorectal cancer liver metastasis by facilitating the phosphorylation and translocation of PKM2
作者机构：Department of General Surgerythe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Colorectal Institute of Nanjing Medical UniversityNanjing 210029China The First School of Clinical MedicineNanjing Medical UniversityNanjing 210029China Jiangsu Province Engineering Research Center of Colorectal Cancer Precision Medicine and Translational MedicineNanjing 210029China
出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)
年 卷 期：2024年第14卷第7期
页 面：2959-2976页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：funded by the National Natural Science Foundation(Grant Number 82273406) Basic Research Program of Jiangsu Province(Grant No.BK20201491,China) Nature Key Research and Development Program of Jiangsu Province(BE2021742,China) Jiangsu Province Capability Improvement Project through Science,Technology and Education(Jiangsu Provincial Medical Key Discipline,ZDXK202222,China) the National Natural Science Foundation(Grant Number 82203656,China)
主 题：CRC CRLM Fructose KHK-A PKM2
摘 要：Excessive fructose diet is closely associated with colorectal cancer(CRC)***,fructose’s specific function and precise mechanism in colorectal cancer liver metastasis(CRLM)is rarely ***,this study reported that the fructose absorbed by primary colorectal cancer could accelerate CRLM,and the expression of KHK-A,not KHK-C,in liver metastasis was higher than in paired primary ***,KHK-A facilitated fructose-dependent CRLM in vitro and in vivo by phosphorylating PKM2 at ***2 phosphorylated by KHK-A inhibited its tetramer formation and pyruvic acid kinase activity but promoted the nuclear accumulation of *** and aerobic glycolysis activated by nuclear PKM2 enhance CRC cells’migration ability and anoikis resistance during CRLM ***-46 treatment,targeting the phosphorylation of PKM2,inhibited the pro-metastatic effect of ***,c-myc activated by nuclear PKM2 promotes alternative splicing of KHK-A,forming a positive feedback loop.
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