Tumor suppressors: enhancers or suppressors of regeneration?

Development. 2013 Jun;140(12):2502-12. doi: 10.1242/dev.084210.

Abstract

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine.

Keywords: Differentiation; Evolution; Regeneration; Tissue homeostasis; Tumor suppressors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Differentiation
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Disease Susceptibility / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Regeneration*
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila
  • PTEN Phosphohydrolase
  • Pten protein, mouse