Related Experiment Video

Updated: Oct 22, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.1K

Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of

Sarra Bouaouiche1,2, Silvia Ghione1,2, Randa Sghaier1,2

  • 1Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), EPHE, PSL Research University, 75000 Paris, France.

International Journal of Molecular Sciences
|August 27, 2021
PubMed

Insights

Glyceryl trinitrate (GTN) inhibits the aggressive properties of triple-negative breast cancer (TNBC) by blocking the JAK2/STAT3 pathway. This study shows GTN

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) is aggressive, invasive, and metastatic, leading to poor patient outcomes.
  • The Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway is crucial for TNBC cell migration, invasion, metastasis, and drug resistance.
  • Interleukin-6 (IL-6) is a key upstream activator of the JAK2/STAT3 pathway.

Purpose of the Study:

  • To investigate the impact of the nitric oxide (NO)-donor glyceryl trinitrate (GTN) on JAK2/STAT3 pathway activation in TNBC cells.
  • To evaluate GTN's effect on TNBC cell migration, invasion, and metastasis in vitro and in vivo.
  • To determine if GTN inhibits JAK2 activation through S-nitrosylation.

Main Methods:

  • Utilized in vitro and in vivo models of TNBC.
  • Activated the JAK2/STAT3 pathway using subtoxic doses of carboplatin and/or recombinant IL-6.
  • Assessed the effects of GTN on JAK2/STAT3 signaling, cell migration, invasion, and lung metastasis.

Main Results:

  • GTN demonstrated an inhibitory effect on JAK2/STAT3 signaling activation in TNBC cells.
  • GTN significantly reduced the migration and invasion capabilities of TNBC cells.
  • GTN was found to inhibit JAK2 activation by mediating its S-nitrosylation.

Conclusions:

  • GTN effectively inhibits the JAK2/STAT3 signaling pathway in TNBC.
  • GTN possesses anti-migratory and anti-invasive properties against TNBC cells.
  • GTN shows potential as an antitumor agent against TNBC metastasis.
Keywords:
cancerinvasionmetastasismigrationnitric oxidesignaling

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.5K
Three-Dimensional 3D Tumor Spheroid Invasion Assay12:19

Three-Dimensional 3D Tumor Spheroid Invasion Assay

Published on: May 1, 2015

58.3K

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.3K
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:
3.2K
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...
4.2K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.6K
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...
4.0K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K