Research Papers:
TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis
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Abstract
Yong Du1,2,#, Lili Liu3,#, Chenliang Wang1,4,5,#, Bohua Kuang2,6, Shumei Yan3, Aijun Zhou2, Chuangyu Wen1,4,5, Junxiong Chen1, Yue Wu1,4,5, Xiangling Yang1, Guokai Feng2, Bin Liu7, Aikichi Iwamoto8,9, Musheng Zeng2, Jianping Wang1, Xing Zhang6, Huanliang Liu1,4,5
1Guangdong 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
2State 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
3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Departments of Pathology and Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
4Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
5Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China
6State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
7Department of Emergency, The Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan, China
8Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
9Current affiliation: Japan Agency for Medical Research and Development (AMED), Tokyo, Japan
#These authors have contributed equally to this work
Correspondence to:
Huanliang Liu, email: [email protected]
Xing Zhang, email: [email protected]
Keywords: colorectal cancer, TACC3, proliferation, migration, invasion
Received: November 10, 2015 Accepted: May 04, 2016 Published: May 26, 2016
ABSTRACT
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.
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