Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes

Cancer Cell. 2004 Jul;6(1):7-10. doi: 10.1016/j.ccr.2004.06.020.


The LKB1 tumor suppressor protein controls the activity of the TSC1/TSC2 tumor suppressor complex. Mutations in LKB1 cause Peutz-Jeghers syndrome (PJS), and mutations in either TSC1 or TSC2 cause tuberous sclerosis complex--two syndromes characterized by the development of hamartomas. LKB1 activation by energy deprivation activates AMPK, which in turn phosphorylates and activates TSC2. TSC2 activation results in the inactivation of mTOR, a critical regulator of protein translation. How mTOR dysregulation after inactivation of LKB1 or TSC1/2 contributes to hamartoma development is not known. However, hypoxia-inducible factor (HIF) and VEGF are regulated by mTOR and are likely to play a contributory role.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Animals
  • DNA-Binding Proteins / metabolism*
  • Hamartoma / genetics
  • Hamartoma / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins / metabolism*
  • Peutz-Jeghers Syndrome / genetics
  • Peutz-Jeghers Syndrome / metabolism*
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases
  • Transcription Factors*
  • Tuberous Sclerosis / genetics
  • Tuberous Sclerosis / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*


  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Protein Kinases
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinase Kinases