This Article Full Text Full Text (PDF) Supplementary Data Correction (v69,p6366) All Versions of this Article: 0008-5472.CAN-08-4135v1 69/13/5364    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by DiMeo, T. A. Articles by Kuperwasser, C. PubMed PubMed Citation Articles by DiMeo, T. A. Articles by Kuperwasser, C.

A Novel Lung Metastasis Signature Links Wnt Signaling with Cancer Cell Self-Renewal and Epithelial-Mesenchymal Transition in Basal-like Breast Cancer

¹ Department of Anatomy and Cellular Biology, Sackler School, Tufts University School of Medicine; ² Molecular Oncology Research Institute and ³ Department of Pathology, Tufts Medical Center, Boston, Massachusetts and ⁴ Departments of Genetics and Pathology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Requests for reprints: Charlotte Kuperwasser, Tufts University School of Medicine, 750 Washington Street, Box 5609, Boston, MA 02111. Phone: 617-636-2364; Fax: 617-636-6127; E-mail: Charlotte.Kuperwasser{at}tufts.edu.

Key Words: breast cancer • wnt • metastasis • EMT

The establishment of metastasis depends on the ability of cancer cells to acquire a migratory phenotype combined with their capacity to recreate a secondary tumor in a distant tissue. In epithelial cancers, such as those of the breast, the epithelial-mesenchymal transition (EMT) is associated with basal-like breast cancers, generates cells with stem-like properties, and enables cancer cell dissemination and metastasis. However, the molecular mechanism(s) that connects stem cell–like characteristics with EMT has yet to be defined. Using an orthotopic model of human breast cancer metastasis to lung, we identified a poor prognosis gene signature, in which several components of the wnt signaling pathway were overexpressed in early lung metastases. The wnt genes identified in this signature were strongly associated with human basal-like breast cancers. We found that inhibiting wnt signaling through LRP6 reduced the capacity of cancer cells to self-renew and seed tumors in vivo. Furthermore, inhibition of wnt signaling resulted in the reexpression of breast epithelial differentiation markers and repression of EMT transcription factors SLUG and TWIST. Collectively, these results provide a molecular link between self-renewal, EMT, and metastasis in basal-like breast cancers. [Cancer Res 2009;69(13):5364–73]

This article has been cited by other articles:

				Correction: Article on Wnt Signaling in Breast Cancer Cancer Res., August 1, 2009; 69(15): 6366 - 6366. [Full Text] [PDF]