A Wnt-ow of opportunity

Targeting the Wnt/β-Catenin pathway in breast cancer

Jenifer Prosperi, Kathleen H. Goss

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Aberrant activation of the Wnt/β-catenin signaling pathway is a hallmark of many tumors, including breast cancer. In the normal breast, tightly regulated expression of Wnt/β-catenin pathway components, including Wnts and the APC tumor suppressor, dictates its role in balancing stem cell self-renewal, maintenance and differentiation during embryonic and postnatal development. Therefore, not surprisingly, dysregulation of Wnt/β-catenin signaling through overexpression of pathway activators, such as Wnts or stabilized β-catenin, or targeted disruption of inhibitors, such as APC, leads to mammary tumorigenesis in several genetically engineered mouse (GEM) models. These models are powerful tools to dissect the importance of Wnt/β-catenin signaling in human breast cancer because they recapitulate some of the histological features of human breast cancers that demonstrate pathway dysregulation. Over the last decade, numerous approaches have been developed to target the Wnt/β-catenin pathway in tumor cells, from antagonizing Wnt ligand secretion or binding to promoting β-catenin degradation to specifically blocking β-catenin-mediated transcriptional activity. Despite sizeable hurdles because of gaps in our knowledge of the most efficacious ways to inhibit the pathway, the breast cancer subtypes to target and how pathway antagonists might be used in combination therapy, crippling Wnt/β- catenin signaling offers a tremendous opportunity to impact breast cancer pathogenesis. This review will provide an overview of the current understanding of Wnt/β-catenin pathway involvement in regulating normal breast development and morphogenesis, the generation of Wnt/β-catenin-dependent GEM models of human breast cancer, upregulation of signaling in human breast cancers and the compelling therapeutic strategies aimed at targeting the Wnt/β-catenin pathway that show promising anti-tumor activity.

Original languageEnglish (US)
Pages (from-to)1074-1088
Number of pages15
JournalCurrent Drug Targets
Volume11
Issue number9
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Catenins
Wnt Signaling Pathway
Breast Neoplasms
Tumors
Breast
Neoplasms
Stem cells
Morphogenesis
Embryonic Development
Carcinogenesis
Up-Regulation

Keywords

  • β-catenin
  • APC
  • Breast cancer
  • Mouse models
  • Wnt

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

A Wnt-ow of opportunity : Targeting the Wnt/β-Catenin pathway in breast cancer. / Prosperi, Jenifer; Goss, Kathleen H.

In: Current Drug Targets, Vol. 11, No. 9, 2010, p. 1074-1088.

Research output: Contribution to journalArticle

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