Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster
Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster
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DOI：
10.1038/ncomms5005
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Hasselblatt, Martin
中科院分区：
文献类型：
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作者：
Jeibmann, Astrid;Eikmeier, Kristin;Hasselblatt, Martin
非典型畸胎样/横纹肌样肿瘤（AT/RT）是恶性脑肿瘤。与大多数其他人类脑肿瘤不同，AT/RT的特征是一个单一基因SMARCB 1的失活。SMARCB 1是进化上保守的SWI/SNF染色质重塑复合物的成员，其在控制细胞分化和增殖中具有重要作用。然而，关于SMARCB 1失活的致癌作用所涉及的途径知之甚少，这也可能代表治疗的靶点。在这里，我们报告了一个全面的遗传筛选果蝇，揭示了几个基因尚未与损失snr 1，果蝇同源SMARCB 1。我们确认了已鉴定基因（包括merlin、kibra和expanded，已知可调节河马信号通路活性）在人横纹肌样肿瘤细胞系和AT/RT肿瘤样本中的功能作用。这些结果表明，苍蝇模型可以用于识别人类癌症中的临床相关途径。
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.