Related Experiment Video

Updated: Nov 5, 2025

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
08:12

The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior

Published on: June 12, 2019

5.3K

Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance

Catalina Lodillinsky1,2, Laetitia Fuhrmann3, Marie Irondelle4

  • 1Research Area, Instituto de Oncología Ángel H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina.

Oncogene
|May 20, 2021
PubMed

Insights

Down-regulation of Nucleoside diphosphate kinase (NME1) accelerates breast cancer invasion by increasing Membrane Type 1 Matrix Metalloprotease (MT1-MMP) levels. Loss of NME1 impairs endocytic clearance, enhancing tumor cell invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Membrane Type 1 Matrix Metalloprotease (MT1-MMP) promotes breast cancer invasion by degrading extracellular matrix.
  • Nucleoside diphosphate kinase (NME1/NM23-H1) is a known metastasis suppressor, but its role in local breast cancer invasion is unclear.

Purpose of the Study:

  • To investigate the role of NME1 in breast cancer local invasion and its relationship with MT1-MMP.
  • To elucidate the molecular mechanisms by which NME1 influences breast cancer cell invasiveness.

Main Methods:

  • Analysis of NME1 and MT1-MMP expression in human breast tissues (DCIS, invasive carcinoma).
  • Correlation analysis between NME1 and MT1-MMP levels in aggressive breast cancers.
  • NME1 knockout studies in an intraductal xenograft model.
  • Investigation of protein interactions at the plasma membrane using co-localization and functional assays.

Main Results:

  • NME1 expression is high in ductal carcinoma in situ (DCIS) and decreases in invasive breast cancer.
  • A strong inverse correlation exists between NME1 and MT1-MMP levels, especially in high-grade and triple-negative breast cancers.
  • NME1 knockout accelerates tumor invasion and increases MT1-MMP surface levels by inhibiting endocytic clearance.
  • NME1 interacts with MT1-MMP and dynamin-2 in clathrin-coated vesicles, regulating MT1-MMP endocytosis.

Conclusions:

  • Down-modulation of NME1 is a key driver of the in situ-to-invasive transition in breast cancer.
  • NME1 regulates MT1-MMP surface levels and activity through endocytic pathway modulation.
  • Targeting NME1 or its interaction with MT1-MMP could offer therapeutic strategies for invasive breast cancer.

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

13.7K
A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer07:35

A Portal Vein Injection Model to Study Liver Metastasis of Breast Cancer

Published on: December 26, 2016

42.0K

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.9K
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...
4.8K
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...
7.2K
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...
4.0K