Insights into targeting LKB1 in tumorigenesis  

作　　者：Charles B.Trelford Trevor G.Shepherd 

机构地区：[1]The Mary&John Knight Translational Ovarian Cancer Research Unit,London Regional Cancer Program,London,ONN6A4L6,Canada [2]Department of Anatomy and Cell Biology,Schulich School of Medicine and Dentistry,Western University,London,ONN6A3K7,Canada [3]Department of Oncology,Schulich School of Medicine and Dentistry,Western University,London,ON N6A 3K7,Canada [4]Department of Obstetrics and Gynaecology,Schulich School of Medicine and Dentistry,Western University,London,ONN6A 3K7,Canada

出　　处：《Genes & Diseases》2025年第2期154-170,共17页基因与疾病(英文)

摘　　要：Genetic alterations to serine-threonine kinase 11(STK11)have been implicated in Peutz-Jeghers syndrome and tumorigenesis.Further exploration of the context-specific roles of liver kinase B1(LKB1;encoded by STK11)observed that it regulates AMP-activated protein ki-nase(AMPK)and AMPK-related kinases.Given that both migration and proliferation are enhanced with the loss of LKB1 activity combined with the prevalence of STK11 genetic alter-ations in cancer biopsies,LKB1 was markedas a tumor suppressor.However,the roleof LKB1 in tumorigenesis is paradoxical as LKB1 activates autophagy and reactive oxygen species scav-enging while dampening anoikis,which contribute to cancer cell survival.Due to the pro-tumor-igenic properties of LKB1,targeting LKB1 pathways is now relevant for cancer treatment.With the recent successes of targeting LKB1 signaling in research and clinical settings,and enhanced cytotoxicity of chemical compounds in LKB1-deficient tumors,there is now a need for LKB1 in-hibitors.However,validating LKB1 inhibitors is challenging as LKB1 adaptor proteins,nucleocy-toplasmic shuttling,and splice variants all manipulate LKB1 activity.Furthermore,STE-20-related kinase adaptor protein(STRAD)and mouse protein 25 dictate LKB1 cellular localization and kinase activity.For these reasons,prior to assessing the efficacy and potency of pharmaco-logical candidates,the functional status of LKB1 needs to be defined.Therefore,to improve the understanding of LKB1 in physiology and oncology,this review highlights the role of LKB1 in tumorigenesis and addresses the therapeutic relevancy of LKB1 inhibitors..

关 键 词：AMPK LKB1 Peutz-Jeghers syndrome STK11 Tumor suppressor 

分 类 号：R73[医药卫生—肿瘤]