Wang Xin, Hankey Pamela A
Graduate Program in Cell and Developmental Biology, The Pennsylvania State University, University Park, Pennsylvania.
Crit Rev Immunol. 2013;33(6):549-74. doi: 10.1615/critrevimmunol.2013007953.
Numerous studies have documented abnormal expression and activation of the Ron receptor tyrosine kinase in a variety of human malignancies. Here we review the literature regarding the molecular mechanisms governing Ron regulation, the biological functions of Ron, the effect of Ron on cancer development, and potential therapeutic implications. In epithelial cells, activation of Ron by its ligand, macrophage stimulating protein, mediates a number of biological events including cell growth, motility, and epithelial to mesenchymal transition. Overexpression and/or activation of Ron has been implicated in the progression and metastasis of diverse epithelial cancers, where it plays a causal role in tumor development by promoting growth, survival, and motility of tumor cells. As a crucial regulator of inflammation, Ron inhibits classic macrophage activation and promotes alternative activation of macrophages, resulting in the resolution of inflammation and tissue repair. In addition, Ron alleviates antitumor immunity by promoting the alternative activation of tumor-associated macrophages, and Ron expression in the tumor microenvironment promotes the outgrowth of metastatic colonies. Hence, Ron is a promising therapeutic target for the treatment of epithelial cancers.
众多研究已证明，Ron受体酪氨酸激酶在多种人类恶性肿瘤中存在异常表达和激活。在此，我们综述了有关Ron调控的分子机制、Ron的生物学功能、Ron对癌症发展的影响以及潜在治疗意义的文献。在上皮细胞中，Ron被其配体巨噬细胞刺激蛋白激活后，介导一系列生物学事件，包括细胞生长、运动以及上皮向间充质转化。Ron的过表达和/或激活与多种上皮癌的进展和转移有关，它通过促进肿瘤细胞的生长、存活和运动，在肿瘤发展中起到因果作用。作为炎症的关键调节因子，Ron抑制经典巨噬细胞激活并促进巨噬细胞的替代性激活，从而导致炎症消退和组织修复。此外，Ron通过促进肿瘤相关巨噬细胞的替代性激活来减轻抗肿瘤免疫，肿瘤微环境中的Ron表达促进转移菌落的生长。因此，Ron是治疗上皮癌的一个有前景的治疗靶点。
