Related Experiment Video

Updated: Nov 18, 2025

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
08:30

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR

Published on: May 16, 2012

24.8K

Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target

Benjamin M Greulich1, Joshua P Plotnik2, Travis J Jerde3

  • 1Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.

NAR Cancer
|February 8, 2021
PubMed

Insights

The TMPRSS2-ERG gene fusion drives prostate cancer. Targeting the toll-like receptor 4 (TLR4) pathway, upstream of ERG, shows promise for treating ERG-positive prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The TMPRSS2-ERG gene fusion is the most common genetic abnormality in prostate cancer, leading to ERG transcription factor overexpression.
  • ERG drives tumor progression, but its function as a transcription factor makes it difficult to target therapeutically.

Purpose of the Study:

  • To identify novel therapeutic targets for ERG-positive prostate cancer.
  • To elucidate the functional relationship between ERG and the toll-like receptor 4 (TLR4) signaling pathway.

Main Methods:

  • Genetic screening to identify pathways critical for ERG function.
  • Utilizing a constitutively active ERG mutant to investigate TLR4 signaling.
  • Employing the TLR4 inhibitor TAK-242 to assess its effects on ERG-driven phenotypes.

Main Results:

  • The toll-like receptor 4 (TLR4) signaling pathway was identified as crucial for ERG function in prostate cells.
  • TLR4 signaling acts upstream to promote ERG phosphorylation at serine 96, enhancing its transcriptional activity.
  • Inhibition of TLR4 with TAK-242 reduced ERG-mediated cell migration, survival, gene activation, and tumor growth.

Conclusions:

  • TLR4 signaling is essential for ERG's oncogenic functions in prostate cancer.
  • Targeting TLR4 represents a potential therapeutic strategy for ERG-positive prostate tumors.

More Related Videos

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer13:19

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

Published on: November 2, 2013

16.9K
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.5K

Related Concept Videos

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...
4.1K
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...
7.4K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.7K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
3.5K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
82.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.5K