title: ROR1 is expressed in human breast cancer and associated with enhanced tumor-cell growth.
abstract: 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.
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Suping
authors.initials: S
authors.lastname: Zhang
authors.forename: Liguang
authors.initials: L
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Cui
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Chuang
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Yu
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang-Rodriguez
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.forename: George
authors.initials: G
authors.lastname: Chen
authors.forename: Grzegorz W
authors.initials: GW
authors.lastname: Basak
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016466:CHO Cells; D049109:Cell Proliferation; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D000911:Antibodies, Monoclonal; D017362:Cyclic AMP Response Element-Binding Protein; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D019869:Phosphatidylinositol 3-Kinases; C078716:ROR1 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D051057:Proto-Oncogene Proteins c-akt