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

• 作者: Wolfgang Link
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: Colon cancer -CATENIN FORKHEAD BOX O3a Metastasis Drug resistance PI3k/AKT INHIBITORS TANKYRASE INHIBITORS Personalized medicine Xenopatient
• 年，卷（期）: 2012,（9）
• 页码范围: 175-179
• 页数: 5页
• 分类号: R735.35

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.