Related Experiment Video

Updated: May 16, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway

Young-Ho Park1, Sun-Uk Kim, Bo-Kyoung Lee

  • 1Disease Model Research Laboratory, Aging Research Center , Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.

Antioxidants & Redox Signaling
|November 29, 2012
PubMed
Abstract

Insights

Peroxiredoxin I (Prx I) suppresses K-ras-driven lung cancer by reducing oxidative stress. Its absence promotes tumor growth via the ROS/ERK/cyclin D1 pathway, highlighting its role as a tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Mutated K-ras and oxidative stress are key factors in non-small-cell lung cancer (NSCLC).
  • The control mechanisms of oxidative stress in K-ras-driven NSCLC are not fully understood.
  • The role of the peroxiredoxin I (Prx I) redox signaling pathway in K-ras(G12D)-mediated lung cancer requires investigation.

Purpose of the Study:

  • To investigate the involvement of the peroxiredoxin I (Prx I) redox signaling pathway in K-ras(G12D)-driven lung adenocarcinogenesis.
  • To determine if Prx I acts as a tumor suppressor in the context of K-ras-driven lung cancer.

Main Methods:

  • Analysis of human lung adenocarcinoma tissues.
  • Utilizing lung-specific K-ras(G12D)-transgenic mouse models.
  • Examining the expression and function of Prx I and its regulation by Nrf2.
  • Assessing the impact of Prx I deficiency on reactive oxygen species (ROS) levels and downstream signaling pathways (ERK/cyclin D1).

Main Results:

  • Prx I is significantly upregulated in lung tumor regions through Nrf2 transcription activation.
  • Loss of Prx I increases ROS levels, promoting K-ras(G12D)-driven lung tumorigenesis in size and number.
  • Increased ROS and tumor growth appear to involve the activation of the ROS-dependent ERK/cyclin D1 pathway.

Conclusions:

  • Prx I acts as an Nrf2-dependently inducible tumor suppressor in K-ras-driven lung adenocarcinogenesis.
  • Prx I opposes the activation of the ROS/ERK/cyclin D1 pathway, thereby inhibiting tumor progression.
  • These findings enhance the understanding of oxidative stress mechanisms in lung tumorigenesis.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

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

Related Concept Videos

The Ras Gene02:38

The Ras Gene

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 superfamily...
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 daughter...
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...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.