Related Experiment Video

Updated: Feb 14, 2026

Transoral Robotic Total Thyroidectomy and Bilateral Central Regional Lymph Node Dissection for Papillary Thyroid Carcinoma
04:01

Transoral Robotic Total Thyroidectomy and Bilateral Central Regional Lymph Node Dissection for Papillary Thyroid Carcinoma

Published on: September 15, 2023

1.6K

Oncogenic mutations in KEAP1 disturbing inhibitory Nrf2-Keap1 interaction: Activation of antioxidative pathway in

Debora Lucia Seguro Danilovic1,2, Evandro Sobroza de Mello3, Eliana Salgado Turri Frazzato1

  • 1Laboratorio de Endocrinologia Celular e Molecular (LIM25), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

Head & Neck
|February 23, 2018
PubMed
Abstract

Insights

Mutations in KEAP1 were found in papillary thyroid carcinomas (PTCs), leading to increased Nrf2 expression. This suggests potential prognostic implications for PTC patients with KEAP1 mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Nuclear factor erythroid 2-like 2 (NFE2L2) encodes Nrf2, a key transcription factor for antioxidative genes.
  • Nrf2 activity is regulated by the Keap1 (Kelch-ECH-associating protein-1) inhibitor complex, which is disrupted by reactive oxygen species.
  • Investigating mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs) can provide insights into disease mechanisms and clinical presentation.

Purpose of the Study:

  • To evaluate the presence of mutations in NFE2L2 and KEAP1 in papillary thyroid carcinomas (PTCs).
  • To correlate these mutations with clinical presentation and histopathological features.
  • To assess the impact of mutations on Nrf2 expression levels.

Main Methods:

  • Sequencing of coding regions of NFE2L2 and KEAP1 in 131 PTC patients.
  • Analysis of clinical and histopathological features.
  • Immunohistochemical analysis of Nrf2 expression in mutated carcinomas.

Main Results:

  • No mutations were found in NFE2L2.
  • Missense mutations in KEAP1 were identified in 4.6% (6/131) of PTC patients.
  • Immunohistochemistry revealed increased nuclear Nrf2 expression in all KEAP1-mutated carcinomas, which exhibited poor prognostic histopathological features.

Conclusions:

  • KEAP1 mutations are associated with Nrf2 overexpression in PTC.
  • These mutations likely disrupt the Nrf2-Keap1 inhibitory interaction, enhancing antioxidant Nrf2 activity.
  • The identified KEAP1 mutations may have prognostic consequences in papillary thyroid carcinomas.
Keywords:
Kelch-ECH-associating protein-1 (KEAP1)NRF2antioxidantmutationthyroid carcinoma

More Related Videos

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma07:01

An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma

Published on: April 17, 2013

21.7K
Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells10:21

Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells

Published on: January 5, 2018

13.7K

Related Concept Videos

Ecological Disturbance02:26

Ecological Disturbance

An ecological disturbance is a temporary disruption in the environment resulting from abiotic, biotic, or anthropogenic factors, causing a pronounced change in an ecosystem. The impact of an ecological disturbance, which can depend on its intensity, frequency, and spatial distribution, plays a significant role in shaping the species diversity within the ecosystem.
21.1K
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
Mutations01:39

Mutations

Overview
94.6K
Papillary Dermis01:11

Papillary Dermis

Dermis
The dermis might be considered the "core" of the integumentary system, as distinct from the epidermis and hypodermis. It contains blood and lymph vessels, nerves, and other structures, such as hair follicles and sweat glands. The dermis is made of two layers of connective tissue that comprise an interconnected mesh of elastin and collagenous fibers, produced by fibroblasts.
Papillary Layer
The papillary layer is made of loose, areolar connective tissue, which means the collagen...
5.9K
Disturbances in Heart Rhythm01:29

Disturbances in Heart Rhythm

Arrhythmia or dysrhythmia refers to an abnormal heart rhythm caused by a defect in the heart's conduction system. It can cause the heart to beat irregularly, too quickly, or too slowly, leading to symptoms like chest pain, shortness of breath, and fainting. Factors such as stress, caffeine, alcohol, nicotine, cocaine, certain drugs, congenital defects, diseases, and electrolyte abnormalities can trigger arrhythmias.
Arrhythmias are categorized by their speed, rhythm, and origin. A slow heart...
3.0K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.0K