Editorial
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Biol Chem. Sep 26, 2012; 3(9): 175-179
Published online Sep 26, 2012. doi: 10.4331/wjbc.v3.i9.175
Nuclear accumulation of β-catenin and forkhead box O3a in colon cancer: Dangerous liaison
Wolfgang Link
Wolfgang Link, Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, 8005-139 Faro, Portugal
Wolfgang Link, IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal
Author contributions: Link W wrote the manuscript
Correspondence to: Wolfgang Link, PhD, Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Gambelas Campus, Building 7, Room 3.17, 8005-139 Faro, Portugal. walink@ualg.pt
Telephone: +351-289-800094 Fax: +351-289-800076
Received: May 11, 2012
Revised: August 22, 2012
Accepted: August 29, 2012
Published online: September 26, 2012
Abstract

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.

Keywords: Colon cancer, β-catenin, Forkhead box O3a, Metastasis, Drug resistance, PI3k/AKT inhibitors, Tankyrase inhibitors, Personalized medicine, Xenopatient