Related Experiment Video

Updated: Feb 28, 2026

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
11:42

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells

Published on: April 7, 2017

9.9K

Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and

Sharleen V Menezes1, Sumit Sahni1, Zaklina Kovacevic1

  • 1Molecular Pharmacology and Pathology Program, Department of Pathology, Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.

The Journal of Biological Chemistry
|June 16, 2017
PubMed

Insights

The metastasis suppressor NDRG1 inhibits cancer-promoting ErbB signaling by blocking EGFR/HER2 and HER2/HER3 heterodimers and degrading EGFR. This finding is crucial for developing new cancer therapies targeting iron and ErbB pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • N-myc downstream-regulated gene 1 (NDRG1) is an iron-regulated metastasis suppressor.
  • NDRG1 inhibits multiple oncogenic signaling pathways in cancer.
  • The ErbB receptor family, including EGFR, HER2, and HER3, are key inducers of carcinogenesis.

Purpose of the Study:

  • To elucidate the inhibitory mechanisms of NDRG1 on ErbB signaling.
  • To understand the role of NDRG1 in regulating EGFR, HER2, and HER3 activity.
  • To explore the therapeutic potential of targeting the interplay between NDRG1, iron, and ErbB signaling.

Main Methods:

  • Investigating NDRG1's effect on ErbB receptor heterodimerization (EGFR/HER2, HER2/HER3).
  • Analyzing NDRG1-mediated down-regulation and degradation of EGFR.
  • Studying the influence of iron regulation on NDRG1's function in cancer cells.

Main Results:

  • NDRG1 inhibits the formation of EGFR/HER2 and HER2/HER3 heterodimers.
  • NDRG1 promotes the degradation of EGFR, thereby attenuating ErbB signaling.
  • NDRG1's inhibitory effects on ErbB signaling are linked to iron regulation.

Conclusions:

  • NDRG1 acts as a critical inhibitor of ErbB signaling pathways crucial for cancer development.
  • Targeting the NDRG1-iron-ErbB axis presents a promising strategy for novel cancer therapies.
  • Further research into this interplay could lead to more effective cancer treatment modalities.
Keywords:
NDRG1cancer therapycell signalingepidermal growth factor receptor (EGFR)ironmetastasis

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

9.4K
Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

36.6K

Related Concept Videos

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...
8.2K
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...
2.9K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
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...
4.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K