Is there more to Wnt signalling in breast cancer than stabilisation of β-catenin?

Giovanna M Collu,Keith Brennan,Olivier Meurette

doi:10.1186/bcr2336

Giovanna M Collu, Keith Brennan + Show 1 more

Open Access

https://doi.org/10.1186/bcr2336

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Journal: Breast Cancer Research	Publication Date: Jul 30, 2009
Citations: 17	License type: cc-by

Affiliation: University of Manchester

Abstract

Increased Wnt signalling has been implicated in the aetiology of many different human cancers, including breast cancers. In most cases, Wnt signalling is thought to drive tumourigenesis through the stabilisation of cytosolic β-catenin and the subsequent changes in the expression of T-cell factor (TCF)-dependent genes. However, this is not necessarily the only mechanism, as Wnt proteins can signal through a number of different intracellular signalling pathways. The ongoing work from Nancy Hynes' laboratory continues to highlight this latter possibility.

Highlights

In their most recent article in Breast Cancer Research, Matsuda and colleagues [1] showed that expression of the secreted Wnt antagonist secreted Frizzled-related protein1 reduced the ability of the breast cancer cell line MDA-MB-231 to form tumours in an orthotopic xenograft model
Using micro-array analysis, they demonstrated that sFRP1 downregulated Cyclin D1 expression, whilst CDKN1A, which encodes the cell cycle regulator p21, was upregulated, leading to an inhibition of proliferation
Wnt1 was the first oncogene to be described in the mammary gland [4] and its potency was reiterated by the ability of Wnt1 to transform primary human mammary epithelial cells alone, unlike the classical oncogenes encoding Ras and SV40 large T antigen, which must act in combination [5]

Summary

Introduction

In their most recent article in Breast Cancer Research, Matsuda and colleagues [1] showed that expression of the secreted Wnt antagonist secreted Frizzled-related protein (sFRP)1 reduced the ability of the breast cancer cell line MDA-MB-231 to form tumours in an orthotopic xenograft model. With this, the inhibition of autocrine Wnt signalling in a panel of breast cancer cell lines led to a reduction in ERK activity and a corresponding inhibition of proliferation [3].

Results

Conclusion