Deregulated E2F Activity as a Cancer-Cell Specific Therapeutic Tool.

Genes (Basel)

Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda, Hyogo 669-1337, Japan.

Published: February 2023

AI Article Synopsis

  • The transcription factor E2F is central to cell growth and tumor suppression, but its activity is often heightened in cancer due to the inactivation of the tumor suppressor pRB.
  • Current cancer treatment trials aim to inhibit E2F activity to slow down cancer cell proliferation, but these methods can also affect normal cells since they rely on the same growth pathways.
  • Deregulated E2F activity, exclusive to cancer cells, activates tumor suppressor genes and is not dependent on growth-stimulating partners, revealing its potential as a targeted cancer therapy.

Article Abstract

The transcription factor E2F, the principal target of the tumor suppressor pRB, plays crucial roles in cell proliferation and tumor suppression. In almost all cancers, pRB function is disabled, and E2F activity is enhanced. To specifically target cancer cells, trials have been undertaken to suppress enhanced E2F activity to restrain cell proliferation or selectively kill cancer cells, utilizing enhanced E2F activity. However, these approaches may also impact normal growing cells, since growth stimulation also inactivates pRB and enhances E2F activity. E2F activated upon the loss of pRB control (deregulated E2F) activates tumor suppressor genes, which are not activated by E2F induced by growth stimulation, inducing cellular senescence or apoptosis to protect cells from tumorigenesis. Deregulated E2F activity is tolerated in cancer cells due to inactivation of the ARF-p53 pathway, thus representing a feature unique to cancer cells. Deregulated E2F activity, which activates tumor suppressor genes, is distinct from enhanced E2F activity, which activates growth-related genes, in that deregulated E2F activity does not depend on the heterodimeric partner DP. Indeed, the ARF promoter, which is specifically activated by deregulated E2F, showed higher cancer-cell specific activity, compared to the E2F1 promoter, which is also activated by E2F induced by growth stimulation. Thus, deregulated E2F activity is an attractive potential therapeutic tool to specifically target cancer cells.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956157PMC
http://dx.doi.org/10.3390/genes14020393DOI Listing

Publication Analysis

Top Keywords

e2f activity
40
deregulated e2f
28
cancer cells
20
e2f
15
tumor suppressor
12
enhanced e2f
12
growth stimulation
12
activity
11
cancer-cell specific
8
therapeutic tool
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!