Liu Yanchun, Yang Hui, Chen Tianxing, Luo Yongbin, Xu Zheyuan, Li Ying, Yang Jiahui
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, China.
Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
PLoS One. 2015 May 15;10(5):e0127092. doi: 10.1371/journal.pone.0127092. eCollection 2015.
Receptor tyrosine kinase ROR1, an embryonic protein involved in organogenesis, is expressed in certain hematological malignancies and solid tumors, but is generally absent in adult tissues. This makes the protein an ideal drug target for cancer therapy. In order to assess the suitability of ROR1 as a cell surface antigen for targeted therapy of lung adenocarcinoma, we carried out a comprehensive analysis of ROR1 protein expression in human lung adenocarcinoma tissues and cell lines. Our data show that ROR1 protein is selectively expressed on lung adenocarcinoma cells, but do not support the hypothesis that expression levels of ROR1 are associated with aggressive disease. However silencing of ROR1 via siRNA treatment significantly down-regulates the activity of the PI3K/AKT/mTOR signaling pathway. This is associated with significant apoptosis and anti-proliferation of tumor cells. We found ROR1 protein expressed in lung adenocarcinoma but almost absent in tumor-adjacent tissues of the patients. The finding of ROR1-mediated proliferation signals in both tyrosine kinase inhibitor (TKI)-sensitive and -resistant tumor cells provides encouragement to develop ROR1-directed targeted therapy in lung adenocarcinoma, especially those with TKI resistance.
受体酪氨酸激酶ROR1是一种参与器官形成的胚胎蛋白，在某些血液系统恶性肿瘤和实体瘤中表达，但在成人组织中通常不存在。这使得该蛋白成为癌症治疗的理想药物靶点。为了评估ROR1作为肺腺癌靶向治疗的细胞表面抗原的适用性，我们对人肺腺癌组织和细胞系中的ROR1蛋白表达进行了全面分析。我们的数据表明，ROR1蛋白在肺腺癌细胞上选择性表达，但不支持ROR1表达水平与侵袭性疾病相关的假设。然而，通过siRNA处理使ROR1沉默可显著下调PI3K/AKT/mTOR信号通路的活性。这与肿瘤细胞的显著凋亡和抗增殖有关。我们发现ROR1蛋白在肺腺癌中表达，但在患者的肿瘤邻近组织中几乎不存在。在酪氨酸激酶抑制剂（TKI）敏感和耐药的肿瘤细胞中均发现了ROR1介导的增殖信号，这为在肺腺癌，尤其是对TKI耐药的肺腺癌中开展ROR1导向的靶向治疗提供了动力。
