A knotty turnabout?: Akt1 as a metastasis suppressor

Cancer Cell. 2005 Dec;8(6):437-9. doi: 10.1016/j.ccr.2005.11.006.

Abstract

Akt is well known to enhance malignancy and is recognized as a key target for antineoplastic therapies. However, intriguing findings reported by Yoeli-Lerner et al. in the November 23, 2005 issue of Molecular Cell, suggest a novel, antimetastasis function of Akt: activation of Akt1 inhibited invasion in some cancer cells. One possible mechanism for this surprising phenotype was that Akt activated the E3 ubiquitin ligase HDM2, causing ubiquitination and degradation of NFAT, an invasion-promoting factor. These findings clearly justify further investigations and, if validated in vivo, call for reevaluation of some Akt-targeting therapeutic strategies currently under development.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Neoplasm Metastasis / physiopathology
  • Neoplasm Metastasis / prevention & control*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-akt / physiology*
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*
  • Ubiquitin / metabolism

Substances

  • NFATC Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Proto-Oncogene Proteins c-akt