Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma

Related Experiment Video

Updated: Jun 12, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Linda Hanlon1, Jacqueline L Avila, Renée M Demarest

  • 1Molecular and Cellular Oncogenesis Program, The Wistar Institute, 3601Spruce Street, Philadelphia, PA 19104, USA.

Cancer Research
|May 21, 2010
PubMed

Insights

Notch1 acts as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Loss of Notch1 accelerates K-ras-induced PDAC development, contrary to previous hypotheses.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • K-ras mutations are prevalent in pancreatic cancer, driving tumorigenesis.
  • Notch1 signaling reactivation is observed in some pancreatic ductal adenocarcinoma (PDAC) cases.
  • Notch1 was hypothesized to function as an oncogene in PDAC.

Purpose of the Study:

  • To investigate the role of Notch1 in K-ras-driven pancreatic tumorigenesis.
  • To determine if Notch1 is essential for the development of PDAC.

Main Methods:

  • Utilized a mouse model with simultaneous activation of oncogenic K-ras and deletion of Notch1 in the pancreas.
  • Observed tumor incidence and progression in the developed mouse model.

Main Results:

  • Loss of Notch1 led to increased tumor incidence.
  • Notch1 deletion accelerated PDAC progression in the K-ras-driven model.
  • Findings contradict the hypothesis of Notch1 acting as an oncogene in PDAC.

Conclusions:

  • Notch1 functions as a tumor suppressor gene in pancreatic ductal adenocarcinoma.
  • The role of Notch1 in PDAC is context-dependent and may vary with K-ras activation.

More Related Videos

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector05:06

Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector

Published on: February 2, 2021

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

Related Concept Videos

Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...