Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer
Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer
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Her3 在两种信号转导模式中的重要作用：Her2/Her3 和 Met/Her3 在人胃癌增殖中的重要作用。
DOI：
10.1002/mc.22241
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发表时间：
2015-12-01
影响因子：
4.6
通讯作者：
Chen Huanqiu
中科院分区：
文献类型：
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作者：
Yun, Chen;Gang, Li;Chen Huanqiu
多种受体酪氨酸激酶(RTK)信号通路在包括胃癌在内的多种肿瘤中被证实，本研究旨在研究包括Her2、HER3和Met在内的多种受体酪氨酸激酶在人胃癌中的表达及其转导模式。免疫组织化学证实HER2、HER3和c-Met在人GC中高表达，导致RTK信号通路的结构性激活。RTKs的联合表达是判断GC患者预后不良的有价值的指标。使用ErbB2特异性抑制剂Lapatinib和c-Met特异性抑制剂PHA-665752，我们进一步证明了这种结构性的RTK信号激活对于GC细胞的生存是必要的。然而，在通过AKT和MAPK信号转导的生长刺激中，存在多种RTK模式：HER3/Her2和Met/HER3。此外，还获得了HER3在两种异源二聚体中的重要作用，在体外和体内都显示了由于HER3被敲除而显著减弱的生长效应。综上所述，HER2/HER3和Met/HER3两种分子转导模式在人胃癌中得到证实，HER3可能成为治疗胃癌的潜在靶点。(C)2014年威利期刊公司。
Various receptor tyrosine kinase (RTK) pathways were verified in many cancers including gastric cancer (GC), We sought to investigate the expression of RTKs including Her2, Her3, and Met and their transduction patterns in human GC. Over-expression of Her2, Her3, and c-Met in human GC was verified by immunohistochemistry leading to constitutive activation of RTK signaling pathways. Combined RTKs expression was valuable indicators for poor prognosis of GC patients. Using ErbB2 specific inhibitor Lapatinib and c-Met specific inhibitor PHA-665752, we further demonstrated that this constitutive activation of RTK signaling is necessary for the survival of GC cells. However, various RTK pattern: Her3/Her2 and Met/Her3 were verified in the transduction growth stimulus from outside via both AKT and MAPK signaling. Moreover, the essential roles of Her3 in both two heterodimers were obtained which showed significantly attenuated growth effect due to Her3 knockdown both in vitro and in vivo. In conclusion, various molecular transduction patterns: Her2/Her3 and Met/Her3 were verified in human GC, and Her3 could serve as a potential target in GC treatment. (c) 2014 Wiley Periodicals, Inc.