TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma.
TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma.
复制标题
TACC3 促进干性，是肝细胞癌的潜在治疗靶点。
DOI：
10.18632/oncotarget.4643
复制
发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Zeng MS
中科院分区：
文献类型：
--
作者：
Zhou DS;Wang HB;Zhou ZG;Zhang YJ;Zhong Q;Xu L;Huang YH;Yeung SC;Chen MS;Zeng MS
转化酸性卷曲蛋白3(TACC3)是细胞有丝分裂和转录功能所必需的。在本研究中，我们首先通过蛋白质印迹分析、免疫组织化学(IHC)和实时定量聚合酶链式反应(qRT-PCR)检测，证实了TACC3蛋白和mRNA在肝细胞癌组织中的表达均高于非癌组织。此外，TACC3高表达与总生存率(OS)和无瘤生存率(DFS)呈正相关(p<；0.001)。在肝癌细胞系中，我们证明了无论是TACC3基因敲除还是潜在的TACC3抑制剂KHS101处理都抑制了细胞的生长和球体形成以及干细胞转录因子Bmi1、c-Myc和Nanog的表达。沉默TACC3可能抑制调节肿瘤干细胞样特性的Wnt/β-连环蛋白和PI3K/AKT信号通路。综上所述，这些数据表明，TACC3在肝癌中丰富，TACC3下调抑制了肝癌细胞的增殖、克隆形成和肿瘤干细胞样表型。TACC3抑制剂KHS101可能成为治疗TACC3高表达的肝癌患者的一种新的治疗药物。
Transforming acidic coiled-coil protein 3 (TACC3) is essential for cell mitosis and transcriptional functions. In the present study, we first demonstrated that both TACC3 protein and mRNA levels were elevated in HCC tissue samples compared with non-cancerous tissue biopsies according to western blot analyses, immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Moreover, high TACC3 expression was positively correlated with poor overall survival (OS) and disease-free survival (DFS) (p < 0.001). Using HCC cell lines, we then demonstrated that either TACC3 knockdown or treatment with the potential TACC3 inhibitor KHS101 suppressed cell growth and sphere formation as well as the expression of stem cell transcription factors, including Bmi1, c-Myc and Nanog. Silencing TACC3 may suppress the Wnt/β-catenin and PI3K/AKT signaling pathways, which regulate cancer stem cell-like characteristics. Taken together, these data suggest that TACC3 is enriched in HCC and that TACC3 down-regulation inhibits the proliferation, clonogenicity, and cancer stem cell-like phenotype of HCC cells. KHS101, a TACC3 inhibitor, may serve as a novel therapeutic agent for HCC patients with tumors characterized by high TACC3 expression.