A role for iron in Wnt signalling.

Abstract:

:There is an emerging body of evidence implicating iron in carcinogenesis and in particular colorectal cancer, but whether this involves Wnt signalling, a major oncogenic signalling pathway has not been studied. We aimed to determine the effect of iron loading on Wnt signalling using mutant APC (Caco-2 and SW480) and wild-type APC (HEK-293 and human primary fibroblasts) containing cell lines. Elevating cellular iron levels in Caco-2 and SW480 cells caused increased Wnt signalling as indicated by increased TOPFLASH reporter activity, increased mRNA expression of two known targets, c-myc and Nkd1, and increased cellular proliferation. In contrast wild-type APC and beta-catenin-containing lines, HEK 293 and human primary fibroblasts were not responsive to iron loading. This was verified in SW480 cells that no longer induced iron-mediated Wnt signalling when transfected with wild-type APC. The cell line LS174T, wild type for APC but mutant for beta-catenin, was also responsive suggesting that the role of iron is to regulate beta-catenin. Furthermore, we show that E-cadherin status has no influence on iron-mediated Wnt signalling. We thus speculate that excess iron could exacerbate tumorigenesis in the background of APC loss, a common finding in cancers.

journal_name

Oncogene

journal_title

Oncogene

authors

Brookes MJ,Boult J,Roberts K,Cooper BT,Hotchin NA,Matthews G,Iqbal T,Tselepis C

doi

10.1038/sj.onc.1210711

subject

Has Abstract

pub_date

2008-02-07 00:00:00

pages

966-75

issue

7

eissn

0950-9232

issn

1476-5594

pii

1210711

journal_volume

27

pub_type

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