Small proline-rich repeat protein 3 enhances the sensitivity of esophageal cancer cells in response to DNA damage-induced apoptosis
Small proline-rich repeat protein 3 enhances the sensitivity of esophageal cancer cells in response to DNA damage-induced apoptosis
复制标题
富含脯氨酸的小重复蛋白3增强食管癌细胞对DNA损伤诱导的细胞凋亡的敏感性
DOI：
10.1016/j.molonc.2013.05.005
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发表时间：
2013-10-01
影响因子：
6.6
通讯作者：
Liu, Zhihua
中科院分区：
文献类型：
--
作者：
Luo, Aiping;Chen, Hongyan;Liu, Zhihua
富含脯氨酸的小重复蛋白3(SPRR3)与化疗放射敏感性的改变有关，但其潜在的分子机制仍不清楚。在此，我们报道了SPRR3的异位过表达增强了细胞对DNA损伤诱导的细胞凋亡的敏感性，这是通过线粒体膜电位的丧失和caspase 3的激活来实现的。相反，下调SPRR3的siRNA可减少细胞凋亡。我们发现SPRR3在体内定位于线粒体并与Bc1-2相互作用，从而促进Bax线粒体易位和随后细胞色素c的释放，从而增强细胞对DNA损伤刺激的敏感性。在临床标本中，SPRR3的表达与局部晚期食管鳞癌患者的病理反应(放疗组P=0.007，术前放疗组P=0.035)和患者的良好生存有关(P=0.008)。综上所述，我们的结果提示，SPRR3可能是ESCC的辐射敏感性预测因子。(C)2013年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Small proline-rich repeat protein 3 (SPRR3) has been linked with the altered chemoradiosensitivity, however the underlying molecular mechanisms remain elusive. Here, we report that ectopic overexpression of SPRR3 enhanced the sensitivity of cells in response to DNA damage-induced apoptosis via loss of mitochondrial membrane potential (MMP), and increasing activation of caspase 3 in human esophageal cancer cell lines. Conversely, siRNA knockdown of SPRR3 reduced apoptosis. We found that SPRR3 was localized in mitochondria and interacted with Bc1-2 in vivo, thus facilitating Bax mitochondrial translocation and the subsequent release of cytochrome c, and thereby enhancing cell sensitivity to DNA damage stimuli. In clinical samples, expression of SPRR3 was associated with the pathologic response (P = 0.007 in radiotherapy group, P = 0.035 in preoperative radiotherapy group) and good survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC, P = 0.008). Taken together, our results implicate that SPRR3 might serve as a radiation-sensitive predictor of ESCC. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.