Related Experiment Video

Updated: Jan 14, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.8K

Inhibiting NEDD4 in triple-negative breast cancer cells reprograms tumor immune microenvironment via the

Nan Su1, Wenhua Lian1, Baoding Zhang1

  • 1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China; State-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian 361102, China; Cancer Research Center of Xiamen University, Xiamen 361102, China.

Cell Reports. Medicine
|October 22, 2025
PubMed

Insights

Targeting NEDD4, an E3 ubiquitin ligase, can convert "cold" triple-negative breast cancer (TNBC) tumors into "hot" tumors. Inhibiting NEDD4 enhances CD8+ T cell infiltration, offering a promising new TNBC treatment strategy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The tumor immune microenvironment critically impacts triple-negative breast cancer (TNBC) progression.
  • Converting "cold" tumors to "hot" tumors is a key therapeutic goal for improving treatment outcomes.
  • NEDD4, a HECT-type E3 ubiquitin ligase, is implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of NEDD4 in TNBC progression and immune cell infiltration.
  • To explore NEDD4 as a potential therapeutic target for enhancing anti-tumor immunity in TNBC.
  • To elucidate the molecular mechanisms by which NEDD4 influences the tumor microenvironment.

Main Methods:

  • Correlation analysis of NEDD4 expression with TNBC patient prognosis and CD8+ T cell infiltration.
  • In vitro studies involving NEDD4 depletion in TNBC cells.
  • Mechanistic studies investigating the β-TrCP/YAP/ECM pathway.
  • In vivo efficacy studies using a small-molecule NEDD4 inhibitor (XMU-MP-10) in mouse models.

Main Results:

  • High NEDD4 expression correlates with poor prognosis and reduced CD8+ T cell infiltration in TNBC.
  • NEDD4 depletion inhibits tumor growth by enhancing CD8+ T cell-mediated cytotoxicity.
  • NEDD4 inhibition stabilizes β-TrCP, leading to YAP ubiquitination and degradation, which reprograms the ECM to increase CD8+ T cell infiltration.
  • The NEDD4 inhibitor XMU-MP-10 demonstrated significant in vivo efficacy in TNBC mouse models.

Conclusions:

  • NEDD4 plays a crucial role in regulating the tumor immune microenvironment in TNBC.
  • Genetic depletion or pharmacological inhibition of NEDD4 enhances anti-tumor immune responses.
  • The β-TrCP/YAP/ECM pathway is a key mechanism mediating NEDD4's effects.
  • Targeting NEDD4 represents a promising therapeutic strategy for TNBC treatment.
Keywords:
E3 ubiquitin ligaseantitumor immunitytriple-negative breast cancertumor microenvironment

More Related Videos

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells10:04

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

Published on: August 1, 2025

1.5K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.4K

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
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...
2.8K
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...
7.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.5K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K
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...
5.1K