LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy

Chia-Chen Liu, Julie Prior, David Piwnica-Worms, Guojun D Bu

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

The Wnt/β-catenin signaling pathway is activated in breast cancer, a leading cause of cancer mortality in women. Because mutations in the key intracellular components of this pathway are rare, identifying the molecular mechanisms of aberrant Wnt activation in breast cancer is critical for development of pathway-targeted therapy.Here, we show that expression of the Wnt signaling coreceptor LRP6 is upregulated in a subpopulation of human breast cancers. LRP6 silencing in breast cancer cells reduces Wnt signaling, cell proliferation, and in vivo tumor growth. In vivo administration of an LRP6 antagonist, Mesd, markedly suppressed growth of MMTV-Wnt1 tumors without causing undesirable side effects. These results demonstrate that Wnt activation at the cell surface contributes to breast cancer tumorigenesis. Together, our studies highlight LRP6 as a potential therapeutic target in breast cancer, and introduce Mesd as a promising antitumor agent for treating breast cancer subtypes with Wnt activation at the cell surface.

Original languageEnglish (US)
Pages (from-to)5136-5141
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number11
DOIs
StatePublished - Mar 16 2010
Externally publishedYes

Fingerprint

Breast Neoplasms
Therapeutics
Catenins
Neoplasms
Wnt Signaling Pathway
Critical Pathways
Growth
Antineoplastic Agents
Carcinogenesis
Cell Proliferation
Mutation
Mortality

Keywords

  • Gene silencing
  • Mesd
  • Proliferation
  • Tumorigenesis
  • Wnt signaling

ASJC Scopus subject areas

  • General

Cite this

LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy. / Liu, Chia-Chen; Prior, Julie; Piwnica-Worms, David; Bu, Guojun D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 11, 16.03.2010, p. 5136-5141.

Research output: Contribution to journalArticle

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