Connexins as precocious markers and molecular targets for chemical and pharmacological agents in carcinogenesis.
Gap junctions, intercellular channels structured by the connexin protein family, have been implicated in the control of cell homeostasis, proliferation, differentiation and death. A loss of the gap junction intercellular communication and/or connexin dysfunction are typical features of cancer per se and have been associated with the effect of many carcinogens. Indeed, many early human neoplasia of various organs and human tumor cell lines exhibit deficient connexin-mediated communication expression mainly related, in a large number of observations, with an aberrant cytoplasmic localization of this membranous protein. Restoration of normal phenotype in transformed cells by restoration of exogenous connexin gave rise to the concept that connexins may act as tumor suppressors. However, the mechanisms by which connexins mediate such a tumor suppressor effect are multiple. They may result from: formation of functional channels; hemichannels or are directly associated with connexin expression. In addition, the literature shows that they may be dependent upon the cell type and the connexin type. In the present review, we analyze all these aspects of connexin/gap junction involvement in the carcinogenesis process, in human cancers and discuss the possibility of using connexins as potential anti-oncogenic targets for cancer chemoprevention and/or chemotherapy.
Pointis
G
G
INSERM U 670, Faculté de Médecine, 27 avenue de Valombrose, 06107 Nice cedex 02, France. pointis@unice.fr
Fiorini
C
C
Gilleron
J
J
Carette
D
D
Segretain
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017630:Connexins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control
D000970:Antineoplastic Agents; D017630:Connexins