The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies.
The MST1R/RON Tyrosine Kinase in Cancer: Oncogenic Functions and Therapeutic Strategies.
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MST 1 R/罗恩受体酪氨酸激酶是存在于上皮细胞、巨噬细胞上的高度保守的跨膜蛋白，并且最近在T细胞亚群中鉴定。罗恩活化减弱健康组织中的炎症。有趣的是，它在几种上皮肿瘤中过表达，表达水平的增加与更差的结果相关。尽管涉及的机制仍在研究中，但罗恩通过免疫肿瘤微环境的免疫调节、许多致癌途径的激活参与致癌作用，并且在细胞应激下具有保护作用。或者，抑制罗恩可消除动物和人组织模型中的肿瘤进展。鉴于此，罗恩是癌症治疗中非常感兴趣的可靶向蛋白。在这里，我们回顾罗恩在组织炎症和癌症进展中的作用，并回顾迄今为止使用靶向罗恩信号传导的药物的癌症临床试验。MST 1 R/罗恩受体酪氨酸激酶是更熟知的MET受体的同源物。与MET一样，罗恩协调促进肿瘤发生并使癌细胞存活的细胞信号通路;然而，它在炎症调节中具有更独特的作用。罗恩最初被描述为在组织驻留巨噬细胞和各种上皮细胞上表达的跨膜受体。罗恩在多种癌症中过表达，并且其活化修饰多种信号传导途径，导致上皮细胞和免疫细胞的变化，这些变化共同调节致癌表型。虽然已经鉴定了几种罗恩同种型在结构、活化和途径调节方面存在差异，但增加的罗恩表达和/或活化始终与更差的结果相关。已经开发了靶向罗恩的酪氨酸激酶抑制剂，使得罗恩成为可操作的治疗靶标。
MST1R/RON receptor tyrosine kinase is a highly conserved transmembrane protein present on epithelial cells, macrophages, and recently identified in a T-cell subset. RON activation attenuates inflammation in healthy tissue. Interestingly, it is overexpressed in several epithelial neoplasms with increasing levels of expression associated with worse outcomes. Though the mechanisms involved are still under investigation, RON is involved in carcinogenesis via immune modulation of the immune tumor microenvironment, activation of numerous oncogenic pathways, and is protective under cellular stress. Alternatively, inhibition of RON abrogates tumor progression in both animal and human tissue models. Given this, RON is a targetable protein of great interest for cancer treatment. Here, we review RON’s function in tissue inflammation and cancer progression, and review cancer clinical trials to date that have used agents targeting RON signaling. The MST1R/RON receptor tyrosine kinase is a homologue of the more well-known MET receptor. Like MET, RON orchestrates cell signaling pathways that promote oncogenesis and enable cancer cell survival; however, it has a more unique role in the regulation of inflammation. RON was originally described as a transmembrane receptor expressed on tissue resident macrophages and various epithelial cells. RON is overexpressed in a variety of cancers and its activation modifies multiple signaling pathways with resultant changes in epithelial and immune cells which together modulate oncogenic phenotypes. While several RON isoforms have been identified with differences in structure, activation, and pathway regulation, increased RON expression and/or activation is consistently associated with worse outcomes. Tyrosine kinase inhibitors targeting RON have been developed, making RON an actionable therapeutic target.
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影响因子：
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作者：
Graves-Deal, Ramona;Bogatcheva, Galina;Singh, Bhuminder
通讯作者：
Singh, Bhuminder
影响因子：
8
作者：
Follenzi, A;Bakovic, S;Comoglio, PM
通讯作者：
Comoglio, PM
影响因子：
--
作者：
Benight NM;Wagh PK;Zinser GM;Peace BE;Stuart WD;Vasiliauskas J;Pathrose P;Starnes SL;Waltz SE
通讯作者：
Waltz SE
影响因子：
11.4
作者：
Fialin, C.;Larrue, C.;Recher, C.
通讯作者：
Recher, C.
影响因子：
3.7
作者：
Chen, YQ;Zhou, YQ;Wang, MH
通讯作者：
Wang, MH