The potential of targeting Sin3B and its associated complexes for cancer therapy

Expert Opin Ther Targets. 2017 Nov;21(11):1051-1061. doi: 10.1080/14728222.2017.1386655. Epub 2017 Oct 9.

Abstract

Sin3B serves as a scaffold for chromatin-modifying complexes that repress gene transcription to regulate distinct biological processes. Sin3B-containing complexes are critical for cell cycle withdrawal, and abrogation of Sin3B-dependent cell cycle exit impacts tumor progression. Areas covered: In this review, we discuss the biochemical characteristics of Sin3B-containing complexes and explore how these complexes regulate gene transcription. We focus on how Sin3B-containing complexes, through the association of the Rb family of proteins, repress the expression of E2F target genes during quiescence, differentiation, and senescence. Finally, we speculate on the potential benefits of the inhibition of Sin3B-containing complexes for the treatment of cancer. Expert opinion: Further identification and characterization of specific Sin3B-containing complexes provide a unique opportunity to prevent the pro-tumorigenic effects of the senescence-associated secretory phenotype, and to abrogate cancer stem cell quiescence and the associated resistance to therapy.

Keywords: Cancer stem cell; Sin3B; cellular senescence; chromatin modifiers; quiescence; senescence associated secretory phenotype.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation / genetics
  • Cellular Senescence / genetics
  • Disease Progression
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Neoplastic Stem Cells / metabolism
  • Repressor Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Repressor Proteins
  • SIN3B protein, human