ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth

• Published in: PloS one Vol. 7; no. 3; p. e31127
• Main Authors: Zhang, Suping, Chen, Liguang, Cui, Bing, Chuang, Han-Yu, Yu, Jianqiang, Wang-Rodriguez, Jessica, Tang, Li, Chen, George, Basak, Grzegorz W, Kipps, Thomas J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.03.2012; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenosine; AKT protein; Animal tissues; Animals; Antibodies, Monoclonal - immunology; Antibody Specificity; Apoptosis; Biology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer research; Cancer therapies; Casein; Casein kinase I; Cell growth; Cell Proliferation; Cell Survival; CHO Cells; Cloning; Cricetinae; Cricetulus; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Dwarfism; Embryogenesis; Embryonic growth stage; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Genomes; Growth; Growth factors; Health aspects; Histograms; Humans; Kinases; Leukemia; Medicine; Mice; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein binding; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Receptor Tyrosine Kinase-like Orphan Receptors - genetics; Receptor Tyrosine Kinase-like Orphan Receptors - immunology; Receptor Tyrosine Kinase-like Orphan Receptors - metabolism; Signal Transduction; Signaling; Transcription factors; Tumor cell lines; Tyrosine; Wnt protein; Wnt Proteins - metabolism; Wnt-5a Protein; La Jolla California; United States > US; California
• DOI: 10.1371/journal.pone.0031127
• ISSN: 1932-6203

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.