Association of tricellulin expression with poor colorectal cancer prognosis and metastasis

Oncol Rep. 2020 Nov;44(5):2174-2184. doi: 10.3892/or.2020.7773. Epub 2020 Sep 17.

Abstract

Tricellulin is a tight‑junction transmembrane protein that regulates cell‑cell interactions. Altered tricellulin expression could promote tumor cell invasions and metastasis in human cancers. The present study assessed tricellulin expression in colorectal cancer tissues for any association with clinicopathological features of colorectal cancer patients and then investigated the underlying molecular events using quantitative proteomic analysis and in vitro experiments. Tissue samples from 98 colorectal cancer patients and 15 volunteers were collected for immunohistochemistry. Colorectal cell lines were used to overexpress or knockdown tricellulin expression in various assays. The data revealed that upregulated tricellulin expression was associated with lymph node and distant metastases and poor prognosis, while tricellulin overexpression promoted colorectal cancer cell migration and invasion in vitro. In contrast, tricellulin knockdown had positive effects on the tumor cells. Furthermore, TMT‑LC‑MS/MS and bioinformatics analyses revealed that tricellulin was involved in EMT and reduction of apoptosis through the NF‑κB signaling pathway. These findings highlight for the first time the significance of tricellulin in colorectal cancer development and progression. Further study may validate tricellulin as a novel biomarker and target for colorectal cancer.

Keywords: colorectal cancer; tricellulin; prognosis; tandem mass tag-liquid chromatography-mass spectrometry.

Publication types

  • Observational Study

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis / pathology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Computational Biology
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Knockdown Techniques
  • Healthy Volunteers
  • Humans
  • Immunohistochemistry
  • MARVEL Domain Containing 2 Protein / analysis
  • MARVEL Domain Containing 2 Protein / genetics
  • MARVEL Domain Containing 2 Protein / metabolism*
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Prognosis
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • MARVEL Domain Containing 2 Protein
  • MARVELD2 protein, human
  • NF-kappa B