ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth
Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is expressed during embryogenesis and by certain leukemias, but not by normal adult tissues. Here we show that the neoplastic cells of many human breast cancers express the ROR1 protein and high-level expression of ROR1 in breast adenocarcinoma...
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Published in | PloS one Vol. 7; no. 3; p. e31127 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
05.03.2012
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is expressed during embryogenesis and by certain leukemias, but not by normal adult tissues. Here we show that the neoplastic cells of many human breast cancers express the ROR1 protein and high-level expression of ROR1 in breast adenocarcinoma was associated with aggressive disease. Silencing expression of ROR1 in human breast cancer cell lines found to express this protein impaired their growth in vitro and also in immune-deficient mice. We found that ROR1 could interact with casein kinase 1 epsilon (CK1ε) to activate phosphoinositide 3-kinase-mediated AKT phosphorylation and cAMP-response-element-binding protein (CREB), which was associated with enhanced tumor-cell growth. Wnt5a, a ligand of ROR1, could induce ROR1-dependent signaling and enhance cell growth. This study demonstrates that ROR1 is expressed in human breast cancers and has biological and clinical significance, indicating that it may be a potential target for breast cancer therapy. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: SZ LC TJK. Performed the experiments: SZ LC GC BC GWB JY LT. Analyzed the data: HYC SZ LC BC GWB TJK. Contributed reagents/materials/analysis tools: JWR. Wrote the paper: SZ TJK LC. Helped evaluate the pathology of human samples: JWR. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0031127 |