Hijacking HES1: how tumors co-opt the anti-differentiation strategies of quiescent cells
- 18 December 2009
- journal article
- review article
- Published by Elsevier BV in Trends in Molecular Medicine
- Vol. 16 (1), 17-26
- https://doi.org/10.1016/j.molmed.2009.11.001
Abstract
Quiescent and tumor cells share the ability to evade irreversible cell fates. Recent studies have shown that the transcriptional regulator Hairy and Enhancer of Split 1 (HES1) protects quiescent fibroblasts from differentiation or senescence. HES1 is highly expressed in rhabdomyosarcomas, and the inhibition of HES1 restores differentiation in these cells. Pathways that lead to elevated HES1 levels, such as the Notch and Hedgehog pathways, are frequently upregulated in tumors. Compounds that inhibit these pathways induce differentiation and apoptosis in cancer cells and several are in clinical trials. HES1 might repress gene expression in part by recruiting histone deacetylases (HDACs). HDACs inhibit differentiation, whereas histone deacetylase inhibitors (HDACis) induce differentiation or apoptosis in tumors and are also showing promise as therapeutics. Small molecules that directly target HES1 itself were recently identified. Here, we discuss the importance of HES1 function in quiescent and tumor cells. Elucidating the pathways that control quiescence could provide valuable information not only for treating cancer but also other diseases.This publication has 110 references indexed in Scilit:
- Inhibition of γ-secretase induces G2/M arrest and triggers apoptosis in breast cancer cellsBritish Journal of Cancer, 2009
- Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulationBritish Journal of Cancer, 2009
- Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinomaClinical & Experimental Metastasis, 2009
- Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancerCancer Letters, 2009
- Emerging role of Notch in stem cells and cancerCancer Letters, 2008
- Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapyCancer Letters, 2008
- Regulation of the Notch target gene Hes-1 by TGFα induced Ras/MAPK signaling in human neuroblastoma cellsExperimental Cell Research, 2005
- Intrinsic tumour suppressionNature, 2004
- The Hallmarks of CancerCell, 2000
- Mutations in the human Sonic Hedgehog gene cause holoprosencephalyNature Genetics, 1996