Connexins in colorectal cancer pathogenesis

Solveig Sirnes, Guro Elisabeth Lind, Jarle Bruun, Tone A. Fykerud, Marc Mesnil, Ragnhild Lothe, Edgar Rivedal, Matthias Kolberg, Edward Leithe

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

The connexins constitute a family of integral membrane proteins that form channels between adjacent cells. These channels are assembled in plasma membrane domains known as gap junctions and enable cells to directly exchange ions and small molecules. Intercellular communication via gap junctions plays important roles in regulating cell growth and differentiation and in maintaining tissue homeostasis. This type of cell communication is often impaired during cancer development, and several members of the connexin protein family have been shown to act as tumor suppressors. Emerging evidence suggests that the connexin protein family has important roles in colorectal cancer development. In the normal colonic epithelial tissue, three connexin isoforms, connexin 26 (Cx26), Cx32 and Cx43, have been shown to be expressed at the protein level. Colorectal cancer development is associated with loss of connexin expression or relocalization of connexins from the plasma membrane to intracellular compartments. Downregulation of connexins in colorectal carcinomas at the transcriptional level involves cancer-specific promoter hypermethylation. Recent studies suggest that Cx43 may constrain growth of colon cancer cells by interfering with the Wnt/β-catenin pathway. There is also increasing evidence that the connexins may have potential as prognostic markers in colorectal cancer. This review discusses the role of connexins in colorectal cancer pathogenesis, as well as their potential as prognostic markers and targets in the prevention and treatment of the disease.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Cancer
Volume137
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

Connexins
Colorectal Neoplasms
Connexin 43
Gap Junctions
Cell Membrane
Catenins
Neoplasms
Wnt Signaling Pathway
Proteins
Ion Exchange
Growth
Cell Communication
Colonic Neoplasms
Cell Differentiation
Protein Isoforms
Membrane Proteins
Homeostasis
Down-Regulation
Epithelium

Keywords

  • Wnt pathway
  • bystander effect
  • colorectal cancer
  • connexins
  • gap junctions
  • intercellular communication
  • prognostic markers
  • β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Connexins in colorectal cancer pathogenesis. / Sirnes, Solveig; Lind, Guro Elisabeth; Bruun, Jarle; Fykerud, Tone A.; Mesnil, Marc; Lothe, Ragnhild; Rivedal, Edgar; Kolberg, Matthias; Leithe, Edward.

In: International Journal of Cancer, Vol. 137, No. 1, 01.07.2015, p. 1-11.

Research output: Contribution to journalReview article

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