Catenins, Wnt signaling and cancer

Bioessays. 2000 Nov;22(11):961-5. doi: 10.1002/1521-1878(200011)22:11<961::AID-BIES1>3.0.CO;2-T.

Abstract

Recent studies indicate that plakoglobin may have a similar function to that of beta-catenin within the Wnt signaling pathway. beta-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs(1) and coworkers show, however, that unlike beta-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of beta-catenin in that it requires activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than beta-catenin, despite its previous identification as a target of Tcf/beta-catenin.(2) In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by beta-catenin than plakoglobin. Plakoglobin and beta-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeletal Proteins / physiology
  • Desmoplakins
  • Neoplasms / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction* / physiology*
  • Trans-Activators*
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin
  • gamma Catenin

Substances

  • Cytoskeletal Proteins
  • Desmoplakins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • gamma Catenin