Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, United States of America.
PLoS One. 2012;7(3):e31127. doi: 10.1371/journal.pone.0031127. Epub 2012 Mar 5.
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.
受体酪氨酸激酶样孤儿受体 1（ROR1）在胚胎发生过程中表达，并存在于某些白血病中，但不存在于正常成人组织中。在这里，我们表明许多人类乳腺癌中的肿瘤细胞表达 ROR1 蛋白，并且乳腺癌腺癌中 ROR1 的高表达与侵袭性疾病相关。沉默在表达这种蛋白的人类乳腺癌细胞系中表达 ROR1 会损害其体外生长，并且在免疫缺陷小鼠中也会损害其生长。我们发现 ROR1 可以与酪蛋白激酶 1 ɛ（CK1ε）相互作用，以激活磷酸肌醇 3-激酶介导的 AKT 磷酸化和 cAMP 反应元件结合蛋白（CREB），从而与增强的肿瘤细胞生长相关。ROR1 的配体 Wnt5a 可以诱导 ROR1 依赖性信号传导并增强细胞生长。这项研究表明 ROR1 在人类乳腺癌中表达，并具有生物学和临床意义，表明它可能是乳腺癌治疗的潜在靶标。
