Nuclear receptor NR4A1 promotes breast cancer invasion and metastasis by activating TGF-β signalling

Related Experiment Video

Updated: May 2, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

13.1K

FangFang Zhou1, Yvette Drabsch2, Tim J A Dekker3

  • 11] Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China [2] Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.

Nature Communications
|March 4, 2014
PubMed

Insights

Nuclear receptor NR4A1 activates the oncogenic TGF-β pathway in breast cancer. Inflammation induces NR4A1, promoting metastasis and indicating poor prognosis, highlighting it as a therapeutic target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • The TGF-β pathway is oncogenic in advanced cancers and a therapeutic target.
  • Nuclear receptors play diverse roles in cellular processes, including cancer.

Purpose of the Study:

  • To identify novel activators of the TGF-β pathway in cancer.
  • To elucidate the role of NR4A1 in TGF-β signaling and breast cancer progression.

Main Methods:

  • Genome-wide cDNA screening to identify NR4A1.
  • Investigating NR4A1's interaction with SMAD7 and AXIN2.
  • Assessing the impact of NR4A1 on TGF-β-induced epithelial-to-mesenchymal transition and metastasis in vitro and in vivo.
  • Analyzing NR4A1 expression in breast cancer patient samples.

Main Results:

  • NR4A1 strongly activates TGF-β/SMAD signaling by promoting SMAD7 degradation via AXIN2-RNF12/ARKADIA.
  • NR4A1 directly induces AXIN2 expression and interacts with SMAD7 and AXIN2.
  • Loss of NR4A1 inhibits metastasis, while its ectopic expression stimulates it in a TGF-β-dependent manner.
  • Inflammatory cytokines induce NR4A1, enhancing breast cancer cell migration, invasion, and metastasis.
  • Elevated NR4A1 expression in patients correlates with high immune infiltration and poor prognosis.

Conclusions:

  • Inflammation-induced NR4A1 is a key driver of pro-oncogenic TGF-β signaling hyperactivation in breast cancer.
  • NR4A1 represents a potential therapeutic target for breast cancer treatment.

More Related Videos

Spheroid Assay to Measure TGF-β-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

20.8K
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.3K

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.6K
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...
7.2K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.6K
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...
3.6K
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...
6.3K
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...
64.6K