Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer
Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer
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细胞膜 gp96 促进 HER2 二聚化并作为乳腺癌的新靶点
DOI：
10.1002/ijc.29405
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发表时间：
2015-08-01
影响因子：
6.4
通讯作者：
Meng, Songdong
中科院分区：
文献类型：
--
作者：
Li, Xin;Sun, Lu;Meng, Songdong
HER2受体二聚化是HER2活化过程中的关键步骤。在这里，我们证明了细胞膜上的热休克蛋白gp96与HER2相互作用，促进HER2二聚化并促进细胞增殖。观察到细胞膜gp96水平与原发性乳腺肿瘤中的HER2磷酸化相关。最后，我们提供的证据表明，靶向gp96与特定的单克隆抗体导致细胞生长减少，细胞凋亡增加，在体外，抑制肿瘤生长在体内。我们的工作代表了抑制癌症中HER2信号传导的新治疗策略。
HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer.