Cell-Permeable Peptide DEPDC1-ZNF224 Interferes with Transcriptional Repression and Oncogenicity in Bladder Cancer Cells
Cell-Permeable Peptide DEPDC1-ZNF224 Interferes with Transcriptional Repression and Oncogenicity in Bladder Cancer Cells
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DOI：
10.1158/0008-5472.can-10-0255
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发表时间：
2010-07-15
期刊：
影响因子：
11.2
通讯作者：
Katagiri, Toyomasa
中科院分区：
文献类型：
--
作者：
Harada, Yosuke;Kanehira, Mitsugu;Katagiri, Toyomasa
膀胱癌是全球第二大常见的泌尿生殖系统癌症，但其致癌起源仍知之甚少。癌-睾丸抗原DEPDC 1最近被证明有助于膀胱癌的发生。在这项研究中，我们研究了DEPDC 1的生物学功能，并确定了一种潜在的治疗策略，以靶向该分子。免疫共沉淀和免疫细胞化学显示DEPDC 1与锌指转录因子ZNF 224（一种已知的转录抑制因子）相互作用并共定位。抑制这种相互作用与细胞渗透肽对应的ZNF 224相互作用域DEPDC 1诱导膀胱癌细胞在体外和体内凋亡。通过抑制DEPDC 1-ZNF 224复合物的形成，该肽触发了NF-κ B信号通路的有效抑制剂A20的转录激活。我们的研究结果表明，DEPDC 1-ZNF 224复合物可能在膀胱癌发生中发挥关键作用。Cancer Res; 70（14）; 5829-39.（C）2010年AACR。
Bladder cancer is the second most common genitourinary cancer worldwide, yet its oncogenic origins remain poorly understood. The cancer-testis antigen DEPDC1 was shown recently to contribute to bladder cancer oncogenesis. In this study, we examined the biological functions of DEPDC1 and defined a potential therapeutic strategy to target this molecule. Coimmunoprecipitation and immunocytochemistry revealed that DEPDC1 interacted and colocalized with zinc finger transcription factor ZNF224, a known transcriptional repressor. Inhibiting this interaction with a cell-permeable peptide corresponding to the ZNF224-interacting domain in DEPDC1 induced apoptosis of bladder cancer cells in vitro and in vivo. By inhibiting DEPDC1-ZNF224 complex formation, this peptide triggered transcriptional activation of A20, a potent inhibitor of the NF-kappa B signaling pathway. Our findings indicate that the DEPDC1-ZNF224 complex is likely to play a critical role in bladder carcinogenesis. Cancer Res; 70(14); 5829-39. (C)2010 AACR.