TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis

Oncotarget. 2016 Jul 5;7(27):41885-41897. 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.

Keywords: TACC3; colorectal cancer; invasion; migration; proliferation.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Male
  • Mice, Nude
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Prognosis
  • RNA Interference
  • RNAi Therapeutics / methods
  • Xenograft Model Antitumor Assays / methods

Substances

  • Microtubule-Associated Proteins
  • TACC3 protein, human