IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1
IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1
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DOI：
10.1038/sj.onc.1209143
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发表时间：
2006-02
期刊：
影响因子：
8
通讯作者：
Y. Sun;D. Gao;Y. Liu;J. Huang;S. Lessnick;S. Tanaka
中科院分区：
文献类型：
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作者：
Y. Sun;D. Gao;Y. Liu;J. Huang;S. Lessnick;S. Tanaka
滑膜肉瘤是一种侵袭性软组织肿瘤，其特征是 18 号染色体和 X 号染色体之间的特定染色体易位。这种易位可以生成编码 SYT-SSX1（一种转化癌蛋白）的融合转录本。我们提供的证据表明 SYT-SSX1 诱导成纤维细胞中胰岛素样生长因子 II 的表达。 SYT-SSX2 是一种在滑膜肉瘤中也常见的融合体，对于维持滑膜肉瘤细胞系中的 Igf2 表达是必需的，并且 IGF2 合成的增加可以保护细胞免受失巢凋亡，并且是体内肿瘤形成所必需的。我们还发现在有限数量的原发性滑膜肉瘤中 Igf2 的印记丢失 (LOI)，尽管 CpG 二核苷酸的去甲基化对于维持印记至关重要。这些发现表明，抑制 IGF2/IGF1-R 信号通路可能是治疗滑膜肉瘤的重要治疗方式。
Synovial sarcoma is an aggressive soft tissue tumor characterized by a specific chromosomal translocation between chromosome 18 and X. This translocation can generate a fusion transcript encoding SYT-SSX1, a transforming oncoprotein. We present evidence that SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells. SYT-SSX2, a fusion also frequently found in synovial sarcoma, is necessary for maintaining Igf2 expression in the synovial sarcoma cell line, and the increased IGF2 synthesis protects cells from anoikis and is required for tumor formation in vivo. We also found a loss of imprinting (LOI) for Igf2 in a limited number of primary synovial sarcomas despite demethylation of CpG dinucleotides critical for maintaining imprinting. These findings suggest that inhibition of the IGF2/IGF1-R signaling pathway may represent a significant therapeutic modality for treating synovial sarcoma.