Contribution of PKB/AKT signaling to thyroid cancer

Front Biosci (Landmark Ed). 2011 Jan 1;16:1461-87. doi: 10.2741/3799.

Abstract

The family of serine/threonine kinases B/Akt (hereafter Akt) represents a central node in signalling pathways downstream of growth factors, cytokines, and other cellular stimuli. In mammalian cells the Akt family comprises three highly homologous members -known as Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma- that regulate several processes including cell proliferation and survival, growth and response to nutrient availability, migration, tissue invasion and angiogenesis. Aberrant activation of Akt is involved in a variety of human cancers including those arising in the thyroid gland. Here, we review the contribution of Akt-dependent pathway in the proliferation of normal thyrocytes, the different pathogenic mechanisms underlying aberrant Akt signalling in thyroid malignancies as well as the relative roles of Akt substrates that most likely contribute to the onset and/or progression of thyroid cancer. Finally, we discuss the current therapeutic strategies targeting the components of the PI3K/Akt pathway in the context of thyroid malignancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / physiology
  • Carcinoma / physiopathology*
  • Carcinoma, Papillary, Follicular / physiopathology
  • Cell Proliferation / drug effects
  • Humans
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / physiology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / physiology
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / physiopathology*
  • ras Proteins / metabolism

Substances

  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • ras Proteins