利用黑腹果蝇鉴定非典型畸胎瘤/横纹肌样瘤生物学相关基因。
Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster.
机构信息
1] Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany [2].
Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149 Münster, Germany.
出版信息
Nat Commun. 2014 Jun 3;5:4005. doi: 10.1038/ncomms5005.
Atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours. Unlike most other human brain tumours, AT/RT are characterized by inactivation of one single gene, SMARCB1. SMARCB1 is a member of the evolutionarily conserved SWI/SNF chromatin remodelling complex, which has an important role in the control of cell differentiation and proliferation. Little is known, however, about the pathways involved in the oncogenic effects of SMARCB1 inactivation, which might also represent targets for treatment. Here we report a comprehensive genetic screen in the fruit fly that revealed several genes not yet associated with loss of snr1, the Drosophila homologue of SMARCB1. We confirm the functional role of identified genes (including merlin, kibra and expanded, known to regulate hippo signalling pathway activity) in human rhabdoid tumour cell lines and AT/RT tumour samples. These results demonstrate that fly models can be employed for the identification of clinically relevant pathways in human cancer.
非典型畸胎样/横纹肌样肿瘤（AT/RT）是一种恶性脑瘤。与大多数其他人类脑瘤不同，AT/RT 的特征是单一基因 SMARCB1 的失活。SMARCB1 是进化上保守的 SWI/SNF 染色质重塑复合物的成员，在控制细胞分化和增殖方面具有重要作用。然而，对于 SMARCB1 失活的致癌作用所涉及的途径知之甚少，这些途径也可能成为治疗的靶点。在这里，我们在果蝇中进行了全面的遗传筛选，揭示了几个尚未与 snr1 相关的基因，snr1 是果蝇中 SMARCB1 的同源物。我们在人类横纹肌瘤细胞系和 AT/RT 肿瘤样本中证实了鉴定出的基因（包括 merlin、kibra 和 expanded，已知它们调节 hippo 信号通路活性）的功能作用。这些结果表明，果蝇模型可用于鉴定人类癌症中具有临床相关性的途径。
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