Related Experiment Video

Updated: Jun 6, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

2.7K

Integrative analysis identifies the atypical repressor E2F8 as a targetable transcriptional activator driving lethal

Furong Huang1, Kexin Li1, Zhong Chen1

  • 1Department of Pathology, Duke University School of Medicine, Durham, NC, USA.

Oncogene
|November 29, 2024
PubMed

Insights

Researchers identified E2F8 as a key driver in lethal prostate cancer, particularly in cases resistant to androgen receptor (AR) therapies. Targeting E2F8 shows promise for inhibiting tumor growth in advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Acquired resistance to androgen receptor (AR)-targeted therapies is a major challenge in treating lethal prostate cancer.
  • Identifying novel therapeutic targets is crucial for improving outcomes in castration-resistant prostate cancer (CRPC).

Purpose of the Study:

  • To screen human transcription factors (TFs) for prognostic significance in CRPC.
  • To identify and characterize novel therapeutic targets for AR-negative CRPC.

Main Methods:

  • Analysis of CRPC datasets from West and East Stand Up to Cancer (SU2C) cohorts to evaluate 1635 TFs.
  • Integrative profiling of E2F8 cistromes and transcriptomes in AR-negative CRPC cells.
  • CRISPR/CasRx system used for E2F8 mRNA knockdown.

Main Results:

  • E2F8 was identified as a TF consistently associated with poorer patient outcomes in CRPC.
  • E2F8 is highly expressed and active in AR-negative CRPC.
  • E2F8 directly activates oncogenes involved in cancer pathways and its knockdown inhibits CRPC growth in vitro and in vivo.

Conclusions:

  • E2F8 is a targetable transcriptional activator driving CRPC, especially AR-negative CRPC.
  • Targeting E2F8 represents a potential therapeutic strategy for advanced prostate cancer.

More Related Videos

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

3.0K
Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH06:26

Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH

Published on: September 20, 2020

3.1K

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K