p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis
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DOI：
10.1016/j.ccr.2005.12.013
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发表时间：
2006-01-01
期刊：
影响因子：
50.3
通讯作者：
Ellisen, LW
中科院分区：
文献类型：
--
作者：
Rocco, JW;Leong, CO;Ellisen, LW
我们证明了Delta Np63α是头颈部鳞状细胞癌(HNSCC)中一个重要的生存因子，它通过抑制依赖于p73的细胞凋亡。RNAi抑制内源性p63的表达可选择性地诱导过表达Delta Np63α的HNSCC细胞的凋亡。P63基因敲除可诱导促凋亡的bcl2家族成员Puma和NoxA，它们的诱导和随后的细胞死亡都不依赖于P53，但需要p73的反式激活。Delta Np63α抑制p73依赖的转录既包括直接的启动子结合，也包括与p73的物理作用。在缺乏内源性Delta Np63α表达的HNSCC细胞中，bc1-2表达上调，可以抑制p73介导的死亡。总之，这些数据定义了一条途径，通过该途径，Delta Np63α通过抑制依赖p73的促凋亡转录程序来提高鳞状上皮恶性肿瘤的存活率。
We demonstrate that Delta Np63 alpha is an essential survival factor in head and neck squamous cell carcinoma (HNSCC) through its ability to suppress p73-dependent apoptosis. Inhibition of endogenous p63 expression by RNAi induces apoptosis selectively in HNSCC cells that overexpress Delta Np63 alpha. Knockdown of p63 induces the proapoptotic bcl-2 family members Puma and Noxa, and both their induction and subsequent cell death are p53 independent but require transactivating isoforms of p73. Inhibition of p73-dependent transcription by Delta Np63 alpha involves both direct promoter binding and physical interaction with p73. In HNSCC cells lacking endogenous Delta Np63 alpha expression, bc1-2 is instead upregulated and can suppress p73-mediated death. Together, these data define a pathway whereby Delta Np63 alpha promotes survival in squamous epithelial malignancy by repressing a p73-dependent proapoptotic transcriptional program.