title: Connexins in colorectal cancer pathogenesis.
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.
authors.affiliation: Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Solveig
authors.initials: S
authors.lastname: Sirnes
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
authors.forename: Jarle
authors.initials: J
authors.lastname: Bruun
authors.forename: Tone A
authors.initials: TA
authors.lastname: Fykerud
authors.forename: Marc
authors.initials: M
authors.lastname: Mesnil
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Edgar
authors.initials: E
authors.lastname: Rivedal
authors.forename: Matthias
authors.initials: M
authors.lastname: Kolberg
authors.forename: Edward
authors.initials: E
authors.lastname: Leithe
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D060449:Wnt Signaling Pathway
chemical_list: D014408:Biomarkers, Tumor; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26
keywords: Wnt pathway; bystander effect; colorectal cancer; connexins; gap junctions; intercellular communication; prognostic markers; β-catenin