DDB2 suppresses tumorigenicity by limiting the cancer stem cell population in ovarian cancer.
DDB2 suppresses tumorigenicity by limiting the cancer stem cell population in ovarian cancer.
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DOI：
10.1158/1541-7786.mcr-13-0638
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Wang QE
中科院分区：
文献类型：
--
作者：
Han C;Zhao R;Liu X;Srivastava A;Gong L;Mao H;Qu M;Zhao W;Yu J;Wang QE
卵巢癌是一种极具侵袭性的疾病，具有很高的肿瘤复发率和化疗耐药性。了解肿瘤复发的潜在机制对卵巢癌的有效治疗至关重要。DNA损伤结合蛋白2 （DNA damage-binding protein 2, DDB2）是一种主要参与核苷酸切除修复的DNA修复因子。在这里，DDB2在卵巢癌细胞的肿瘤发生和卵巢癌患者的预后中被发现了一个新的作用。在人卵巢癌细胞中过表达DDB2抑制了其在胸腺裸鼠中再现肿瘤的能力。机制研究表明，DDB2能够减少卵巢癌细胞中具有高醛脱氢酶活性的癌症干细胞（CSC）群体，可能是通过破坏CSC的自我更新能力。对公开可用的基因表达阵列数据集的分析显示，低DDB2表达与卵巢癌患者的不良预后相关。鉴于发现DDB2蛋白在卵巢肿瘤细胞中的表达较低，增强DDB2表达是一种很有希望的根除CSCs的策略，有助于阻止卵巢癌复发。
Ovarian cancer is an extremely aggressive disease associated with a high percentage of tumor recurrence and chemotherapy resistance. Understanding the underlying mechanism of tumor relapse is crucial for effective therapy of ovarian cancer. DNA damage-binding protein 2 (DDB2) is a DNA repair factor mainly involved in nucleotide excision repair. Here, a novel role was identified for DDB2 in the tumorigenesis of ovarian cancer cells and the prognosis of patients with ovarian cancer. Overexpressing DDB2 in human ovarian cancer cells suppressed its capability to recapitulate tumors in athymic nude mice. Mechanistic investigation demonstrated that DDB2 is able to reduce the cancer stem cell (CSC) population characterized with high aldehyde dehydrogenase activity in ovarian cancer cells, probably through disrupting the self-renewal capacity of CSCs. Low DDB2 expression correlates with poor outcomes among patients with ovarian cancer, as revealed from the analysis of publicly available gene expression array datasets. Given the finding that DDB2 protein expression is low in ovarian tumor cells, enhancement of DDB2 expression is a promising strategy to eradicate CSCs and would help to halt ovarian cancer relapse.