The EphB4 receptor tyrosine kinase promotes lung cancer growth: a potential novel therapeutic target.
The EphB4 receptor tyrosine kinase promotes lung cancer growth: a potential novel therapeutic target.
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DOI：
10.1371/journal.pone.0067668
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Salgia R
中科院分区：
文献类型：
--
作者：
Ferguson BD;Liu R;Rolle CE;Tan YH;Krasnoperov V;Kanteti R;Tretiakova MS;Cervantes GM;Hasina R;Hseu RD;Iafrate AJ;Karrison T;Ferguson MK;Husain AN;Faoro L;Vokes EE;Gill PS;Salgia R
尽管局部和全身治疗取得了进展，但肺癌患者的生存仍然是一个挑战。受体酪氨酸激酶常参与肺癌的发病机制，一些酪氨酸激酶抑制策略在临床上是有效的。EphB4受体酪氨酸激酶最近已成为其他几种癌症的潜在靶点。我们试图系统地研究EphB4在肺癌中的作用。在这里，我们证明了EphB4在肺肿瘤中的过表达是配对正常组织的3倍，并且在肺癌中经常表现出基因拷贝数的增加。我们还表明EphB4的过表达促进细胞增殖、集落形成和运动性，而EphB4抑制降低体外细胞活力，当用作单靶策略时，在小鼠异种移植模型中停止已建立的肿瘤的生长，并且当与紫杉醇组合使用时，导致已建立的肿瘤几乎完全消退。总之，这些数据表明EphB4作为肺癌的潜在新治疗靶点的重要作用。研究抗EphB4疗法以及涉及EphB4抑制的组合疗法的功效的临床试验可能是必要的。
Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.
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