TACC3促进结直肠癌的肿瘤发生,并与不良预后相关。
TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis.
作者信息
Du Yong, Liu Lili, Wang Chenliang, Kuang Bohua, Yan Shumei, Zhou Aijun, Wen Chuangyu, Chen Junxiong, Wu Yue, Yang Xiangling, Feng Guokai, Liu Bin, Iwamoto Aikichi, Zeng Musheng, Wang Jianping, Zhang Xing, Liu Huanliang
机构信息
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology and The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
出版信息
Oncotarget. 2016 Jul 5;7(27):41885-41897. doi: 10.18632/oncotarget.9628.
Colorectal carcinoma (CRC) is a malignant epithelial tumour with tremendous invasion and metastatic capacity. Transforming acidic coiled-coil protein-3 (TACC3), a frequently aberrantly expressed oncogene, is an important biomarker in various human cancers. Our study aimed to investigate the expression and function of TACC3 in human CRC. We found that TACC3 was over-expressed at both the mRNA and protein levels in CRC cells and in biopsies of CRC tissues compared with normal controls as determined by qRT-PCR, western blot and immunohistochemical (IHC) staining assays. IHC staining of samples from 161 patients with CRC also revealed that TACC3 expression was significantly correlated with clinical stage (P = 0.045), T classification (P = 0.029) and M classification (P = 0.020). Multivariate analysis indicated that high TACC3 expression was an independent prognostic marker for CRC. Patients who had high TACC3 expression had significantly poorer overall survival (OS, P = 0.023) and disease-free survival (DFS, P = 0.019) compared to patients who had low TACC3 expression. Furthermore, TACC3 knockdown attenuated CRC cell proliferation, colony formation capability, migration and invasion capability, and tumourigenesis in nude mice; these properties were measured using a real-time cell analyser (RTCA), clonogenicity analysis, and transwell and xenograft assays, respectively. These data indicate that TACC3 promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for CRC.
结直肠癌(CRC)是一种具有极强侵袭和转移能力的恶性上皮性肿瘤。转化酸性卷曲螺旋蛋白3(TACC3)是一种经常异常表达的癌基因,是多种人类癌症中的重要生物标志物。我们的研究旨在探讨TACC3在人类结直肠癌中的表达及功能。通过qRT-PCR、蛋白质印迹法和免疫组织化学(IHC)染色分析,我们发现与正常对照相比,TACC3在结直肠癌细胞和结直肠癌组织活检标本中的mRNA和蛋白质水平均呈过表达。对161例结直肠癌患者的样本进行IHC染色还显示,TACC3表达与临床分期(P = 0.045)、T分级(P = 0.029)和M分级(P = 0.020)显著相关。多因素分析表明,TACC3高表达是结直肠癌的独立预后标志物。与TACC3低表达的患者相比,TACC3高表达的患者总生存期(OS,P = 0.023)和无病生存期(DFS,P = 0.019)明显更差。此外,TACC3基因敲低可减弱结直肠癌细胞的增殖、集落形成能力、迁移和侵袭能力以及裸鼠体内的肿瘤发生;这些特性分别通过实时细胞分析仪(RTCA)、克隆形成分析、Transwell实验和异种移植实验进行检测。这些数据表明,TACC3促进结直肠癌进展,可能是结直肠癌的独立预后因素和潜在治疗靶点。