Overview on how oncogenic Kras promotes pancreatic carcinogenesis by inducing low intracellular ROS levels

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Updated: May 7, 2026

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture
08:16

Mimicking and Manipulating Pancreatic Acinar-to-Ductal Metaplasia in 3-dimensional Cell Culture

Published on: February 11, 2019

Bo Kong1, Chengjia Qia, Mert Erkan

  • 1Department of Surgery, Technische Universität München Munich, Germany.

Frontiers in Physiology
|September 25, 2013
PubMed

Insights

Pancreatic cancer risk may be linked to low reactive oxygen species (ROS) levels. Oncogenic Kras mutations in pancreatic ductal adenocarcinoma (PDAC) promote low ROS, potentially driving cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with unknown causes.
  • Antioxidant supplementation suggests reactive oxygen species (ROS) involvement in pancreatic carcinogenesis.
  • Oncogenic Kras mutations, prevalent in PDAC, paradoxically lead to low intracellular ROS levels.

Purpose of the Study:

  • To investigate the role of low intracellular ROS in Kras-driven pancreatic cancer.
  • To explore the mechanisms by which Kras mutations decrease ROS levels.

Main Methods:

  • Analysis of Kras signaling pathways.
  • Investigation of antioxidant gene expression regulated by Nrf2.
  • Examination of the glutamine metabolic pathway and NADPH generation.
  • Assessment of ROS levels in pancreatic pre-neoplastic and cancer cells.

Main Results:

  • Oncogenic Kras activates Nrf2, increasing antioxidant gene expression.
  • Kras mediates glutamine metabolism to produce NADPH for ROS detoxification.
  • Low intracellular ROS levels are observed in pre-neoplastic and cancerous pancreatic cells.
  • Low ROS is associated with stem cell self-renewal and proliferation.

Conclusions:

  • Low intracellular ROS, driven by oncogenic Kras, may significantly contribute to PDAC development.
  • Kras-induced ROS suppression creates a pro-proliferative environment, supporting cancer stem cell characteristics.
Keywords:
KrasG12Doncogenic Kraspancreatic cancerpancreatic cancer stem cellsreactive oxygen speciesredox equilibrium

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