Related Experiment Video

Updated: Jan 29, 2026

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
07:16

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

Published on: March 14, 2014

14.6K

TMPRSS2-ERG activates NO-cGMP signaling in prostate cancer cells

Feng Zhou1,2,3, Shuai Gao2,3, Dong Han2,3

  • 1Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.

Oncogene
|February 6, 2019
PubMed

Insights

Targeting the soluble guanylyl cyclase (sGC) pathway may offer a new treatment for prostate cancer (PCa) driven by the TMPRSS2-ERG gene fusion. Inhibiting sGC reduced tumor growth and enhanced enzalutamide effectiveness in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The TMPRSS2-ERG gene fusion drives prostate cancer (PCa) via the ERG oncogenic pathway.
  • Identifying therapeutic targets downstream of ERG is crucial for effective PCa treatment.

Purpose of the Study:

  • To investigate the role of soluble guanylyl cyclase (sGC) and its downstream signaling in ERG-driven PCa.
  • To evaluate sGC inhibition as a potential therapeutic strategy for TMPRSS2-ERG-positive PCa.

Main Methods:

  • Assessed sGC subunit expression regulation by ERG in vitro and in vivo.
  • Analyzed the association between sGC expression and TMPRSS2-ERG fusion in clinical PCa samples.
  • Measured cGMP synthesis and protein kinase G (PKG) activity in PCa cells.
  • Evaluated the efficacy of sGC inhibitors, alone and in combination with enzalutamide, in PCa xenograft models.

Main Results:

  • ERG directly regulates the expression of sGC α1 and β1 subunits, which correlates with TMPRSS2-ERG fusion in PCa.
  • ERG-mediated elevation of cGMP synthesis leads to increased PKG activity and PCa cell proliferation.
  • sGC inhibition suppressed tumor growth in preclinical models of TMPRSS2-ERG-positive PCa.
  • Combined sGC inhibition and enzalutamide showed synergistic effects.

Conclusions:

  • ERG-driven upregulation of the NO-cGMP-PKG pathway promotes PCa growth.
  • Targeting sGC represents a promising therapeutic avenue for prostate cancer with TMPRSS2-ERG gene fusion.
  • Combination therapy with sGC inhibitors and androgen receptor antagonists may improve treatment outcomes.

More Related Videos

A New Technique for Treating Low-risk Prostate Cancer—Super Active Surveillance05:19

A New Technique for Treating Low-risk Prostate Cancer—Super Active Surveillance

Published on: November 7, 2025

844
Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells08:03

Generation of Prostate Cancer Patient Derived Xenograft Models from Circulating Tumor Cells

Published on: October 20, 2015

14.6K

Related Concept Videos

What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.3K
Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
54.3K
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...
4.8K
Overview of Cell Signaling01:23

Overview of Cell Signaling

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate with the environment.
Cells respond to many types of information, often through receptor proteins positioned on the membrane. For example, skin cells respond to and transmit touch...
24.7K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.1K
Cell Signaling in Plants01:25

Cell Signaling in Plants

Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
6.2K