Defective downregulation of receptor tyrosine kinases in cancer

EMBO J. 2004 Jul 21;23(14):2707-12. doi: 10.1038/sj.emboj.7600292. Epub 2004 Jul 1.

Abstract

Most growth factors control cellular functions by activating specific receptor tyrosine kinases (RTKs). While overactivation of RTK signalling pathways is strongly associated with carcinogenesis, it is becoming increasingly clear that impaired deactivation of RTKs may also be a mechanism in cancer. A major deactivation pathway, receptor downregulation, involves ligand-induced endocytosis of the RTK and subsequent degradation in lysosomes. A complex molecular machinery that uses the small protein ubiquitin as a key regulator assures proper endocytosis and degradation of RTKs. Here we discuss evidence that implicates deregulation of this machinery in cancer.

Publication types

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

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Down-Regulation*
  • Endocytosis / physiology
  • Endosomal Sorting Complexes Required for Transport
  • Humans
  • Ligands
  • Lysosomes / metabolism
  • Models, Biological
  • Neoplasms / metabolism*
  • Protein Transport
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism
  • Ubiquitin / metabolism

Substances

  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Ligands
  • Transcription Factors
  • Tsg101 protein
  • Ubiquitin
  • Receptor Protein-Tyrosine Kinases