Nuclear accumulation of β-catenin and forkhead box O3a in colon cancer:Dangerous liaison  

作　　者：Wolfgang Link 

机构地区：[1]Regenerative Medicine Program,Department of Biomedical Sciences and Medicine,University of Algarve,8005-139 Faro,Portugal [2]IBB-Institute for Biotechnology and Bioengineering,Centro de Biomedicina Molecular e Estrutural,Universidade do Algarve,Campus de Gambelas,8005-139 Faro,Portugal

出　　处：《World Journal of Biological Chemistry》2012年第9期175-179,共5页世界生物化学杂志（英文版）（电子版）

摘　　要：The WNT/-catenin and phosphoinositide 3-kinase(PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer.Oncogenic PI3K/AKT signaling suppresses the activity of forkhead box O3a(FOXO3a) transcription factor through phosphorylation leading to its nuclear exclusion.Inhibition of the PI3K/AKT signaling by PI3K or AKT inhibitors results in the translocation of FOXO3a to the nucleus,and is considered to be a promising therapeutic strategy for many cancers including colon cancer.Now,however,a new study in Nature Medicine has revealed a nuclear interaction of-catenin with FOXO3a as a promoter of metastatic progression in colon cancer.The work has important implications for the treatment of colon cancers,suggests a companion biomarker strategy to enable a personalized medicine approach,and offers an alternative therapeutic strategy to overcome resistance to PI3K and AKT inhibitors.The WNT/β-catenin and phosphoinositide 3-kinase (PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer. Oncogenic PI3K/AKT signaling suppresses the activity of forkhead box O3a (FOXO3a) transcription factor through phosphorylation leading to its nuclear exclusion. Inhibition of the PI3K/AKT signaling by PI3K or AKT inhibitors results in the translocation of FOXO3a to the nucleus, and is considered to be a promising therapeutic strategy for many cancers including colon cancer. Now, however, a new study in Nature Medicine has revealed a nuclear interaction of β-catenin with FOXO3a as a promoter of metastatic progression in colon cancer. The work has important implications for the treatment of colon cancers, suggests a companion biomarker strategy to enable a personalized medicine approach, and offers an alternative therapeutic strategy to overcome resistance to PI3K and AKT inhibitors.

关 键 词：Colon cancer -CATENIN FORKHEAD BOX O3a Metastasis Drug resistance PI3k/AKT INHIBITORS TANKYRASE INHIBITORS Personalized medicine Xenopatient 

分 类 号：R735.35[医药卫生—肿瘤]