Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both β-catenin dependent and independent Wnt signalling

Henry, C., Quadir, A., Hawkins, N.J., Jary, E., Llamosas, E., Kumar, D., Daniels, B., Ward, R.L. and Ford, C.E. (2015) Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both β-catenin dependent and independent Wnt signalling. Journal of Cancer Research and Clinical Oncology, 141 2: 243-254. doi:10.1007/s00432-014-1824-y

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Author Henry, C.
Quadir, A.
Hawkins, N.J.
Jary, E.
Llamosas, E.
Kumar, D.
Daniels, B.
Ward, R.L.
Ford, C.E.
Title Expression of the novel Wnt receptor ROR2 is increased in breast cancer and may regulate both β-catenin dependent and independent Wnt signalling
Journal name Journal of Cancer Research and Clinical Oncology   Check publisher's open access policy
ISSN 1432-1335
0171-5216
Publication date 2015-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1007/s00432-014-1824-y
Open Access Status Not yet assessed
Volume 141
Issue 2
Start page 243
End page 254
Total pages 12
Place of publication Heidelberg, Germany
Publisher Springer Verlag
Language eng
Formatted abstract
Purpose    Wnt signalling has been implicated in breast cancer, and in particular aberrant β-catenin-independent Wnt signalling has been associated with breast cancer metastasis and Tamoxifen resistance. Despite Wnt pathway involvement in many human cancers, attempts to target the pathway therapeutically have been disappointing. The recent discovery that the receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a novel Wnt receptor provides a potential new therapeutic and diagnostic target.
Methods    To clarify the role of ROR2 in breast cancer, we investigated its expression via ROR2 immunohistochemistry in a clinical cohort of breast cancer patients, and via in vitro studies incorporating both overexpression and knock-down of ROR2.
Results    ROR2 was expressed in the majority of breast cancer patients (87 %), including those classed as triple negative. Breast cancer patients expressing ROR2 had a significantly shorter overall survival than those lacking ROR2 expression (P < 0.05). Overexpression of ROR2 in the mammary epithelial cell line, MCF10A, increased both β-catenin-dependent and β-catenin-independent targets and decreased cell adhesion. Knock-down of ROR2 in the breast cancer cell lines, MDA-MB-453 and HCC1143, decreased both β-catenin-dependent and β-catenin-independent targets and increased cell adhesion. Treatment of ROR2-expressing breast cancer cells with the novel berberine derivative, NAX53, significantly inhibited cell proliferation and migration.
Conclusions    This is the first study to report the expression of ROR2 in breast cancer. Breast cancer patients expressing ROR2 had a significantly worse prognosis than those lacking ROR2. ROR2 may regulate both β-catenin-dependent and β-catenin-independent Wnt signalling pathways, and represents a potential diagnostic and therapeutic target.
Keyword ROR2
Wnt signalling
Breast cancer
Metastasis
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 630458
Institutional Status UQ
Additional Notes Published online 11 September 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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