Related Experiment Video

Updated: May 10, 2026

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis
07:43

Intracarotid Cancer Cell Injection to Produce Mouse Models of Brain Metastasis

Published on: February 8, 2017

Complex I protein NDUFB9 is a metabolic vulnerability in triple negative breast cancer brain metastases

Mingxi Lin1,2, Zhexu Wen3, Cheng Zeng1,2

  • 1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Nature Communications
|May 8, 2026
PubMed

Insights

Targeting NDUFB9 offers a new strategy for triple-negative breast cancer brain metastases (TNBC BrMs). This approach exploits a brain-specific metabolic vulnerability to selectively inhibit BrM growth by disrupting aspartate metabolism.

Area of Science:

  • Oncology
  • Metabolic pathways
  • Cancer metastasis

Background:

  • Triple-negative breast cancer brain metastases (TNBC BrMs) present significant therapeutic challenges.
  • Understanding the metabolic differences between primary tumors and brain metastases is crucial for developing targeted therapies.

Purpose of the Study:

  • To identify brain-specific metabolic vulnerabilities in TNBC BrMs.
  • To elucidate the mechanisms underlying TNBC BrM growth and develop targeted therapeutic strategies.

Main Methods:

  • Comparative analysis of primary tumors and BrMs.
  • Metabolomic profiling of patient-matched cerebrospinal fluid and plasma.
  • High-throughput in vivo CRISPR loss-of-function screens to identify key genes.

Main Results:

  • NDUFB9 (NADH: Ubiquinone Oxidoreductase Subunit B9) was identified as a brain-specific metabolic vulnerability.
  • NDUFB9 knockout selectively inhibited BrM outgrowth without affecting extracranial metastases.
  • A dual-hit mechanism involving aspartate depletion and compensatory asparagine biosynthesis was elucidated, leading to suppressed nucleotide synthesis and BrM growth.

Conclusions:

  • NDUFB9 is a promising therapeutic target for TNBC BrMs.
  • Targeting NDUFB9 exploits a unique metabolic vulnerability in the brain microenvironment.
  • This strategy offers a selective approach to suppress TNBC brain metastasis growth.

More Related Videos

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells05:02

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Published on: February 4, 2021

Related Concept Videos

Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...