Wang Ming-Hai, Yao Hang-Ping, Zhou Yong-Qing
Laboratory of Chang-Kung Scholars Program for Tumor Biology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Acta Pharmacol Sin. 2006 Jun;27(6):641-50. doi: 10.1111/j.1745-7254.2006.00361.x.
Recepteur d'origine nantais (RON) belongs to a subfamily of receptor tyrosine kinases (RTK) with unique expression patterns and biological activities. RON is activated by a serum-derived growth factor macrophage stimulating protein (MSP). The RON gene transcription is essential for embryonic development and critical in regulating certain physiological processes. Recent studies have indicated that altered RON expression contributes significantly to cancer progression and malignancy. In primary tumors, such as colon and breast cancers, overexpression of RON exists in large numbers and is often accompanied by the generation of different splicing variants. These RON variants direct a unique program that controls cell transformation, growth, migration, and invasion, indicating that altered RON expression has the ability to regulate motile/invasive phenotypes. These activities were also seen in transgenic mice, in which targeted expression of RON in lung epithelial cells resulted in numerous tumors with pathological features of human bronchioloalveolar carcinoma. Thus, abnormal RON activation is a pathogenic factor that transduces oncogenic signals leading to uncontrolled cell growth and subsequent malignant transformation. Considering these facts, RON and its variants can be considered as potential targets for therapeutic intervention. Experiments using small interfering RNA and neutralizing monoclonal antibodies demonstrated that suppressing RON expression and activation decreases cancer cell proliferation, increases apoptotic death, prevents tumor formation in nude mice, and reduces malignant phenotypes. Thus, blocking RON expression and activation has clinical significance in reversing malignant phenotypes and controlling tumor growth.
源自南特的受体（RON）属于受体酪氨酸激酶（RTK）亚家族，具有独特的表达模式和生物学活性。RON由血清衍生的生长因子巨噬细胞刺激蛋白（MSP）激活。RON基因转录对胚胎发育至关重要，在调节某些生理过程中起关键作用。最近的研究表明，RON表达改变对癌症进展和恶性程度有显著影响。在原发性肿瘤，如结肠癌和乳腺癌中，大量存在RON的过表达，且常伴有不同剪接变体的产生。这些RON变体指导一个独特的程序，控制细胞转化、生长、迁移和侵袭，表明RON表达改变有能力调节运动性/侵袭性表型。在转基因小鼠中也观察到了这些活性，其中在肺上皮细胞中靶向表达RON导致出现许多具有人类细支气管肺泡癌病理特征的肿瘤。因此，异常的RON激活是一种致病因素，可转导致癌信号，导致细胞不受控制地生长并随后发生恶性转化。考虑到这些事实，RON及其变体可被视为治疗干预的潜在靶点。使用小干扰RNA和中和单克隆抗体的实验表明，抑制RON表达和激活可降低癌细胞增殖、增加凋亡死亡、防止裸鼠肿瘤形成并减少恶性表型。因此，阻断RON表达和激活在逆转恶性表型和控制肿瘤生长方面具有临床意义。
