Principles of tumor suppression

Cell. 2004 Jan 23;116(2):235-46. doi: 10.1016/s0092-8674(03)01075-4.


Molecular genetic studies of familial cancer syndromes identified and defined the recessive nature of tumor suppressor genes and resolved the paradox of why tumors arising in such families exhibited an autosomally dominant pattern of inheritance. Subsequent characterization of tumor suppressor proteins revealed their widespread involvement in sporadic cancers and pinpointed key mechanisms that protect animals against tumor development. We now recognize that tumor suppressor genes regulate diverse cellular activities, including cell cycle checkpoint responses, detection and repair of DNA damage, protein ubiquitination and degradation, mitogenic signaling, cell specification, differentiation and migration, and tumor angiogenesis. Their study has become a centerpiece of contemporary cancer research.

Publication types

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

MeSH terms

  • ADP-Ribosylation Factors / physiology
  • Cell Cycle
  • Cell Differentiation
  • Cell Movement
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Damage
  • DNA Repair
  • Genes, Tumor Suppressor*
  • Genetic Predisposition to Disease
  • Ligands
  • Models, Biological
  • Neoplasms / etiology
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / physiology
  • Ubiquitin / metabolism


  • Cyclin-Dependent Kinase Inhibitor p16
  • Ligands
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Ubiquitin
  • ADP-Ribosylation Factors