TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis.

Yong Du,Guokai Feng,Lili Liu,Huanliang Liu,Shumei Yan,Chuangyu Wen,Musheng Zeng,Xing Zhang,Aikichi Iwamoto,Chenliang Wang,Jianping Wang,Bohua Kuang,Xiangling Yang,Junxiong Chen,Bin Liu,Yue Wu,Aijun Zhou

doi:10.18632/oncotarget.9628

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.

Highlights

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, being responsible for approximately 1.4 million cases and 0.7 million deaths in 2012 [1]
We found that both the mRNA and protein levels of Transforming acidic coiled-coil protein-3 (TACC3) were increased in the CRC samples compared with normal control samples (Figure 1B, 1D)
This result was further confirmed by IHC staining, which showed strong expression of TACC3 in cancer cells (Figure 2A, 2C) and negative or weak expression in adjacent normal cells (Figure 2A, 2B) from the same patient specimens

Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, being responsible for approximately 1.4 million cases and 0.7 million deaths in 2012 [1]. Tumour markers, such as somatic mutations in BRAF and KRAS, have been used to characterize CRC epidemiology and to guide clinical decision-making. New biomarkers must be identified to further characterize BRAF or KRAS mutation-negative colorectal tumours. The referenced studies have revealed that TACC3 mainly promotes tumour progression by enhancing cell proliferation, cancer stem cell populations and cancer cell migration [12, 14]. In several types of tumours, a common TACC3 fusion gene known as FGFR3-TAAC3 has been shown to promote the development of cancer cells by promoting cell proliferation [17,18,19]

Methods

Results

Conclusion