Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

7.6K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.8K
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...
3.8K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

2.6K
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...
2.6K
Abnormal Proliferation02:23

Abnormal Proliferation

4.6K
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...
4.6K
The Ras Gene02:38

The Ras Gene

6.3K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.3K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

5.7K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Meeting Report From the 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting, Amsterdam, the Netherlands, October 2025.

Pigment cell & melanoma research·2026
Same author

eIF4G2-Dependent Translation Restrains Pancreatic Cancer Progression.

Cancer research·2026
Same author

A MAFG~MITF complex drives melanoma phenotype switching and progression.

Nature communications·2026
Same author

Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency.

Nature chemical biology·2026
Same author

PHGDH is a targetable driver of PDAC progression.

bioRxiv : the preprint server for biology·2026
Same author

Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells.

Nature metabolism·2026

Related Experiment Video

Updated: Aug 2, 2025

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
07:39

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Published on: June 16, 2018

9.3K

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation and Progression.

Janine M DeBlasi1,2, Aimee Falzone1, Samantha Caldwell1

  • 1Department of Metabolism & Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Cancer Research
|April 16, 2023
PubMed
Summary

Mutations in the KEAP1-NRF2 pathway are common in non-small cell lung cancer. NRF2 stabilization promotes early tumor growth but hinders later progression, showing context-dependent effects.

More Related Videos

Lung Tumor Cell Recruitment Assay
04:28

Lung Tumor Cell Recruitment Assay

Published on: February 26, 2019

5.4K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.0K

Related Experiment Videos

Last Updated: Aug 2, 2025

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues
07:39

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues

Published on: June 16, 2018

9.3K
Lung Tumor Cell Recruitment Assay
04:28

Lung Tumor Cell Recruitment Assay

Published on: February 26, 2019

5.4K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.0K

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Mutations in the KEAP1-NRF2 pathway are prevalent in non-small cell lung cancer (NSCLC), correlating with therapeutic resistance and poor prognosis.
  • The KEAP1-NRF2 pathway regulates cellular defense mechanisms and is frequently dysregulated in various cancers.

Purpose of the Study:

  • To investigate the precise role of KEAP1 and NRF2 mutations in NSCLC initiation and progression using murine models.
  • To determine the context-dependent and threshold-dependent effects of NRF2 activation in lung tumorigenesis.

Main Methods:

  • Development of murine alleles mimicking human KEAP1 and NRF2 mutations found in NSCLC.
  • Comprehensive analysis of tumor initiation and progression in genetically engineered mouse models.
  • Assessment of NRF2 overexpression effects on KEAP1-mutant human NSCLC cell lines.

Main Results:

  • Constitutive NRF2 activation alone or with p53/LKB1 loss did not induce tumorigenesis.
  • NRF2 activation with KrasG12D/+ promoted early tumor initiation but inhibited progression to advanced-grade tumors.
  • NRF2 deletion reversed the inhibitory effect on advanced tumor progression.
  • NRF2 overexpression was detrimental to the proliferation and viability of KEAP1-mutant NSCLC cells.

Conclusions:

  • NRF2 stabilization has context-dependent and threshold-dependent roles in lung tumorigenesis, promoting initiation but blocking progression.
  • The KEAP1-NRF2 pathway's activity threshold is critical for its function in different stages of lung cancer development.