Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Res. 2012 Mar 15;72(6):1547-56. doi: 10.1158/0008-5472.CAN-11-3222. Epub 2012 Feb 8.

Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling.

Author information

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. david.horst@med.uni-muenchen.de

Abstract

Colorectal cancers (CRC) express the WNT effector protein β-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor-initiating capability. CRC cells with the highest WNT levels showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust mitogen-activated protein kinase (MAPK) signaling, which when upregulated by KRAS expression or downregulated by epidermal growth factor receptor inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Furthermore, they suggest that MAPK signaling is a critical modifier of intratumoral heterogeneity that contributes significantly to determining the impact of WNT activity on stemness phenotypes in colon cancer cells.

PMID:
22318865
[PubMed - indexed for MEDLINE]
PMCID:
PMC3571091
Free PMC Article

Images from this publication.See all images (4)Free text

Figure 1
Figure 2
Figure 3
Figure 4
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk