Related Experiment Video

Updated: Jul 2, 2026

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
09:16

Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy

Published on: September 11, 2015

Feedback inhibitors of the epidermal growth factor receptor signaling pathways

Noriko Gotoh1

  • 1Division of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan. ngotoh@ims.u-tokyo.ac.jp

The International Journal of Biochemistry & Cell Biology
|September 3, 2008
PubMed

Insights

Negative regulators of epidermal growth factor receptor (EGFR) signaling fine-tune cell growth. Downregulation of these inhibitors promotes cancer, suggesting their potential as biomarkers and therapeutic targets for personalized medicine.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Epidermal growth factor receptor (EGFR) family tyrosine kinases are crucial for cell proliferation and migration, and their dysregulation contributes to tumorigenesis.
  • Negative regulators of EGFR signaling networks play a vital role in maintaining cellular homeostasis.
  • Downregulation of these negative regulators can lead to aberrant EGFR signaling, promoting cancer development.

Purpose of the Study:

  • To review specific feedback inhibitors that target EGFR.
  • To discuss the multiple modes of action of these inhibitors.
  • To explore the potential of these inhibitors as cancer biomarkers and therapeutic targets.

Main Methods:

  • Literature review of feedback inhibitors targeting EGFR.
  • Analysis of the roles of specific inhibitors including mitogen-inducible gene-6 (Mig-6), fibroblast growth factor receptor substrate 2beta (FRS2beta), suppressor of cytokine signaling 3 (SOCS3), and leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1).

Main Results:

  • Identified several key feedback inhibitors of EGFR signaling: Mig-6, FRS2beta, SOCS3, and LRIG1.
  • These inhibitors exhibit diverse mechanisms for regulating EGFR activity.
  • Fragmentary evidence suggests their potential utility.

Conclusions:

  • These EGFR feedback inhibitors represent promising avenues for cancer biomarker development.
  • Targeting these inhibitors therapeutically could advance personalized medicine approaches for cancer treatment.

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

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

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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
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 activation may...
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 are of three kinds RI, RII, and RIII. The RI...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: