表皮生长因子受体（EGFR）野生型拮抗胶质母细胞瘤中EGFRvIII介导的间质上皮转化因子（Met）激活。
EGFR wild type antagonizes EGFRvIII-mediated activation of Met in glioblastoma.
作者信息
Li L, Puliyappadamba V T, Chakraborty S, Rehman A, Vemireddy V, Saha D, Souza R F, Hatanpaa K J, Koduru P, Burma S, Boothman D A, Habib A A
机构信息
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Oncogene. 2015 Jan 2;34(1):129-134. doi: 10.1038/onc.2013.534. Epub 2013 Dec 23.
Epidermal growth factor receptor (EGFR)vIII is the most common EGFR mutant found in glioblastoma (GBM). EGFRvIII does not bind ligand, is highly oncogenic and is usually coexpressed with EGFR wild type (EGFRwt). EGFRvIII activates Met, and Met contributes to EGFRvIII-mediated oncogenicity and resistance to treatment. Here, we report that addition of EGF results in a rapid loss of EGFRvIII-driven Met phosphorylation in glioma cells. Met is associated with EGFRvIII in a physical complex. Addition of EGF results in a dissociation of the EGFRvIII-Met complex with a concomitant loss of Met phosphorylation. Consistent with the abrogation of Met activation, addition of EGF results in the inhibition of EGFRvIII-mediated resistance to chemotherapy. Thus, our study suggests that ligand in the milieu of EGFRvIII-expressing GBM cells is likely to influence the EGFRvIII-Met interaction and resistance to treatment, and highlights a novel antagonistic interaction between EGFRwt and EGFRvIII in glioma cells.
表皮生长因子受体（EGFR）vIII是胶质母细胞瘤（GBM）中最常见的EGFR突变体。EGFRvIII不结合配体，具有高度致癌性，通常与野生型EGFR（EGFRwt）共表达。EGFRvIII激活Met，而Met有助于EGFRvIII介导的致癌性和耐药性。在此，我们报告添加表皮生长因子（EGF）会导致胶质瘤细胞中EGFRvIII驱动的Met磷酸化迅速丧失。Met与EGFRvIII在一个物理复合物中相关联。添加EGF会导致EGFRvIII-Met复合物解离，同时Met磷酸化丧失。与Met激活的消除一致，添加EGF会导致对EGFRvIII介导的化疗耐药性的抑制。因此，我们的研究表明，表达EGFRvIII的GBM细胞环境中的配体可能会影响EGFRvIII-Met相互作用和耐药性，并突出了胶质瘤细胞中EGFRwt和EGFRvIII之间一种新的拮抗相互作用。
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