CDH4 is a novel determinant of osteosarcoma tumorigenesis and metastasis
CDH4 is a novel determinant of osteosarcoma tumorigenesis and metastasis
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CDH4是骨肉瘤肿瘤发生和转移的新决定因素
DOI：
10.1038/s41388-018-0231-2
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发表时间：
2018-07-05
期刊：
影响因子：
8
通讯作者：
Khokha, Rama
中科院分区：
文献类型：
--
作者：
Tang, Qinglian;Lu, Jinchang;Khokha, Rama
癌症基因组学的时代现在提供了一个机会，发现骨肉瘤（OS）的新决定因素，骨肉瘤是儿童和青少年中最常见的原发性骨癌，因肺转移而预后不良。在这里，我们使用阵列CGH鉴定了43.6%的人骨肉瘤中的CDH 4扩增，并证明了其在骨肉瘤发展和进展中的关键作用。编码R-钙粘蛋白的CDH 4的功能的获得或丧失会因果地影响人OS细胞的多种特征，包括细胞迁移和侵袭、成骨分化和干性。CDH 4过表达通过JNK途径激活c-Jun，而CDH 4敲低抑制肿瘤异种移植物生长和肺定殖。在OS患者标本中，高CDH 4表达与肺转移和预后不良相关。总的来说，我们的生物信息学、功能、分子和临床分析揭示了CDH 4在骨肉瘤中的致癌功能及其与患者预后的关系。
The era of cancer genomics now provides an opportunity to discover novel determinants of osteosarcoma (OS), the most common primary bone cancer in children and adolescents known for its poor prognosis due to lung metastasis. Here, we identify CDH4 amplification in 43.6% of human osteosarcoma using array CGH and demonstrate its critical role in osteosarcoma development and progression. Gain or loss-of-function of CDH4, which encodes R-cadherin, causally impacts multiple features of human OS cells including cell migration and invasion, osteogenic differentiation, and stemness. CDH4 overexpression activates c-Jun via the JNK pathway, while CDH4 knockdown suppresses both tumor xenograft growth and lung colonization. In OS patient specimens, high CDH4 expression associates with lung metastases and poor prognosis. Collectively, our bioinformatics, functional, molecular, and clinical analyses uncover an oncogenic function of CDH4 in osteosarcoma and its relationship with patient outcome.