CDCA3 promotes cell proliferation by activating the NF-κB/cyclin D1 signaling pathway in colorectal cancer

Biochem Biophys Res Commun. 2018 Jun 2;500(2):196-203. doi: 10.1016/j.bbrc.2018.04.034. Epub 2018 Apr 14.

Abstract

Cell division cycle associated 3 (CDCA3) is required for mitotic entry, and mediates the degradation of the inhibitory kinase Wee1. New evidence suggests CDCA3 plays a role in tumor promotion. However, little is known about the relevance of CDCA3 in colorectal cancer(CRC), especially in the regulation of NF-κB activity. In this study, we found that colorectal tumors significantly expressed more CDCA3 than non-cancer tissues. In addition, CDCA3 promoted CRC cell proliferation in vitro. Furthermore, downregulation of CDCA3 not only induced cell cycle arrest but also facilitated apoptosis. Mechanistically, CDCA3 activates the NF-κB signaling pathway by interacting with TRAF2 in CRC. Together, these results define a tumor-supportive role for CDCA3, which may also provide a new promising strategy for treating CRC.

Keywords: CDCA3; Colorectal cancer; Cyclin D1; NF-κB signaling pathway; Proliferation; TRAF2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Signal Transduction*
  • TNF Receptor-Associated Factor 2 / metabolism
  • Up-Regulation / genetics

Substances

  • CCND1 protein, human
  • CDCA3 protein, human
  • Cell Cycle Proteins
  • NF-kappa B
  • TNF Receptor-Associated Factor 2
  • Cyclin D1