Open AccessNuclear accumulation of β-catenin and forkhead box O3a in colon cancer: Dangerous liaison
Author(s) -
Wolfgang Link
Publication year - 2012
Publication title -
world journal of biological chemistry
Language(s) - English
Resource type - Journals
ISSN - 1949-8454
DOI - 10.4331/wjbc.v3.i9.175
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , wnt signaling pathway , colorectal cancer , medicine , cancer research , catenin , foxo1 , cancer , signal transduction , bioinformatics , biology , microbiology and biotechnology
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.