High PLK4 expression promotes tumor progression and induces epithelial‑mesenchymal transition by regulating the Wnt/β‑catenin signaling pathway in colorectal cancer

Int J Oncol. 2019 Feb;54(2):479-490. doi: 10.3892/ijo.2018.4659. Epub 2018 Dec 10.

Abstract

Polo‑like kinase 4 (PLK4) has been identified as an oncogene, which is overexpressed in various types of human cancer; however, its role in colorectal cancer (CRC) development remains unknown. The present study demonstrated that PLK4 protein expression was upregulated in CRC tissues compared with in normal tissues through western blotting. In addition, immunohistochemical analysis of 39 CRC specimens further demonstrated that PLK4 protein expression was upregulated in 64.1% (25/39) of samples. Increased PLK4 expression was closely associated with enhanced tumor size (P=0.031), lymph node metastasis (P=0.016) and TNM stage (P=0.001). Subsequently, cell viability, wound scratch, migration and invasion assays were conducted in vitro, and nude mice CRC xenograft models were generated. The results demonstrated that knockdown of PLK4 in CRC cells resulted in significant decreases in cell viability and proliferation, and decreased the protein expression levels of N‑cadherin and snail, which are biomarkers of epithelial‑mesenchymal transition. Furthermore, PLK4 knockdown inactivated the Wnt/β‑catenin pathway in CRC cells in vitro and in vivo, and suppressed the growth of xenograft tumors in nude mice. In conclusion, these results suggested that PLK4 may promote the carcinogenesis and metastasis of CRC, thus indicating that PLK4 may be considered a molecular target for CRC treatment.

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Wnt Signaling Pathway*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • PLK4 protein, human
  • Plk4 protein, mouse
  • Protein Serine-Threonine Kinases