Related Experiment Video

Updated: Jun 9, 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

5.9K

NRF3 suppresses the malignant progression of TNBC by promoting M1 polarization of macrophages via ROS/HMGB1 axis

Ping Xing1,2, Zhenzhen Chen3, Wenbo Zhu1,2

  • 1Department of Surgical Oncology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.

Cancer Biology & Therapy
|October 24, 2024
PubMed
Abstract

Insights

Nuclear respiratory factor 3 (NRF3) inhibits triple-negative breast cancer (TNBC) progression by promoting M1 macrophage polarization via the ROS/HMGB1 pathway. NRF3 may serve as a novel therapeutic biomarker for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
  • Nuclear respiratory factor 3 (NRF3) and high-mobility group box 1 (HMGB1) roles in TNBC progression are under investigation.
  • Understanding TNBC mechanisms is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of NRF3 in TNBC progression.
  • To elucidate the molecular mechanisms underlying NRF3's function in TNBC.
  • To explore NRF3 as a potential therapeutic biomarker for TNBC.

Main Methods:

  • Utilized TCGA database and bioinformatics for NRF3 expression and immune infiltration analysis in TNBC.
  • Performed in vitro assays (MTT, colony formation, transwell, flow cytometry, western blotting) to assess TNBC cell functions.
  • Employed immunofluorescence, IHC, qRT-PCR, CHIP, luciferase, and ELISA assays to determine NRF3 regulatory functions.
  • Established a xenograft model to evaluate NRF3's in vivo role in TNBC.

Main Results:

  • Low NRF3 expression correlated with poor prognosis in TNBC patients.
  • NRF3 overexpression suppressed malignant phenotypes, MAPK/ERK signaling, and epithelial-mesenchymal transition (EMT).
  • NRF3 promoted reactive oxygen species (ROS) production, facilitating HMGB1 release and M1 macrophage polarization, thereby inhibiting TNBC progression.

Conclusions:

  • NRF3 inhibits TNBC malignancy by promoting M1 macrophage polarization through the ROS/HMGB1 axis.
  • NRF3 demonstrates potential as a therapeutic biomarker for triple-negative breast cancer.
  • Targeting the NRF3 pathway could offer novel therapeutic strategies for TNBC.
Keywords:
HMGB1NRF3ROSTriple-negative breast cancermacrophages

More Related Videos

Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line06:38

Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line

Published on: August 2, 2021

27.2K
Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity08:41

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

Published on: June 7, 2017

8.2K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
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...
7.2K
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
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:
1.3K
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
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K