Ou Yunwei, Liu Lingyan, Xue Liyan, Zhou Wei, Zhao Zitong, Xu Bainan, Song Yongmei, Zhan Qimin
Department of Neurosurgery, Chinese PLA General Hospital, Beijing 100853, China; State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
J Genet Genomics. 2014 Oct 20;41(10):529-37. doi: 10.1016/j.jgg.2014.08.004. Epub 2014 Sep 3.
Tumor necrosis factor receptor-associated protein 1 (TRAP1), an important member of mitochondrial heat shock protein 90 family, is involved in multiple biological processes in several types of tumors. However, its pathological role in esophageal squamous cell cancer (ESCC) remains unknown. Herein, we demonstrated the clinical value of TRAP1, and its role in apoptosis and motility in ESCC. The clinical potential of TRAP1 was investigated through immunohistochemical analysis in 328 ESCC samples, which revealed that strong TRAP1 expression was associated with increased risk of lymph node metastasis, while high TRAP1 expression correlated with poor prognosis. Expression of TRAP1 was found to be an independent prognostic factor for patients with ESCC. Additionally, the upregulation of TRAP1 antagonized cisplatin-induced apoptosis while its downregulation sensitized cells to cisplatin-induced apoptosis. As revealed by the transwell assay, TRAP1 overexpression promoted cellular migration and invasion as compared to the control groups. In contrast, silencing of endogenous TRAP1 expression attenuated the ability of migration and invasion. Finally, the molecular mechanism investigated in the present study demonstrated that TRAP1-mediated migration and invasion occurred through STAT3/MMP2 signaling pathway. In conclusion, TRAP1 may be considered as a molecular predictive marker for prognosis and a novel molecular candidate for therapeutic target in ESCC.
肿瘤坏死因子受体相关蛋白1（TRAP1）是线粒体热休克蛋白90家族的重要成员，参与多种类型肿瘤的多个生物学过程。然而，其在食管鳞状细胞癌（ESCC）中的病理作用尚不清楚。在此，我们阐述了TRAP1在ESCC中的临床价值及其在凋亡和运动性方面的作用。通过对328例ESCC样本进行免疫组织化学分析，研究了TRAP1的临床潜力，结果显示TRAP1的高表达与淋巴结转移风险增加相关，而TRAP1的高表达与预后不良相关。发现TRAP1的表达是ESCC患者的独立预后因素。此外，TRAP1的上调拮抗顺铂诱导的凋亡，而其下调使细胞对顺铂诱导的凋亡敏感。通过Transwell实验表明，与对照组相比，TRAP1过表达促进细胞迁移和侵袭。相反，内源性TRAP1表达的沉默减弱了迁移和侵袭能力。最后，本研究中研究的分子机制表明，TRAP1介导的迁移和侵袭通过STAT3/MMP2信号通路发生。总之，TRAP1可被视为ESCC预后的分子预测标志物和治疗靶点的新型分子候选物。
