title: Gap junctional communication and neoplastic transformation.
abstract: Gap junctional communication (GJC) is mediated by channels consisting of connexins and can be differentially regulated by ions, second messengers, kinases, phosphatases, and cell adhesion molecules. Tumor cells and oncogene-transformed cells often, but not always, show reduced homologous GJC between themselves. A more stringent correlation may exist between transformation and reduced heterologous communication between transformed cells and normal neighbors. Reduced GJC seems to stimulate tumor promotion but has no significant effect on the initiation phase of carcinogenesis. These effects may reflect the importance of intercellular passage of second messengers or other small molecules in cell growth control. Some evidence suggests that gap junction in combination with cell adhesion molecules can affect metastatic potential, but a clear picture has not yet emerged. Coupling and gap junction expression can be regulated both pre- and posttranslationally in oncogene-transformed cells. Src probably downregulates GJC in fibroblasts by tyrosine phosphorylation of connexin43. The Ras-induced reduction in GJC appears to be caused by decreased connexin expression. E1A, but not Myc and Fos, downregulates GJC to some extent. Artificial expression of connexin in glioma, hepatoma, chemically transformed, and src-transformed cells can restore GJC and suppress growth and/or tumorigenesis. These results argue for involvement of GJC in transformation and growth control.
authors.affiliation: Department of Pathology, Cornell University, Ithaca, NY 14853.
authors.forename: A
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.forename: D
authors.initials: D
authors.lastname: Shalloway
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017630:Connexins / Q000096:biosynthesis*; D017629:Gap Junctions / Q000502:physiology*; D018014:Gene Transfer Techniques; D006801:Humans; D009362:Neoplasm Metastasis; D009857:Oncogenes
chemical_list: D017630:Connexins