Related Experiment Video

Updated: Jul 18, 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

Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer

V Fernández-Majada1, C Aguilera, A Villanueva

  • 1Centre Oncologia Molecular, Institut d'Investigació Biomèdica de Bellvitge, Gran Via Km 2.7, Hospitalet, 08907 Barcelona, Spain.

Proceedings of the National Academy of Sciences of the United States of America
|December 28, 2006
PubMed

Insights

Nuclear functions of IkappaB kinase (IKK) are revealed in colorectal cancer. IKK activation releases SMRT corepressor from Notch targets, promoting tumor growth, but inhibition reduces tumor size.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Nuclear functions of IkappaB kinase (IKK), including histone H3 and corepressor phosphorylation, are emerging.
  • Aberrant cytoplasmic localization of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) is observed in colorectal tumors.

Purpose of the Study:

  • To investigate the role of IKK in colorectal cancer progression.
  • To elucidate the mechanism of SMRT corepressor regulation by IKK in colorectal tumors.

Main Methods:

  • Analysis of IKK activation and SMRT localization in colorectal tumors.
  • Chromatin immunoprecipitation assays to study IKKalpha-chromatin association.
  • Inhibition of IKK activity using BAY11-7082 and dominant-negative IKKalpha.
  • Gene expression analysis of Notch target genes.
  • Assessment of tumor growth in colorectal cancer xenografts (CRC-Xs).

Main Results:

  • IKK activation in colorectal tumors correlates with cytoplasmic SMRT.
  • IKKalpha associates with chromatin of specific Notch targets, causing SMRT release.
  • IKK inhibition restores SMRT association with target genes, leading to repression.
  • BAY11-7082 treatment significantly reduces tumor size in CRC-Xs.

Conclusions:

  • IKK plays a critical role in colorectal cancer by regulating SMRT corepressor localization and activity.
  • IKK-mediated SMRT release from Notch targets promotes tumor progression.
  • Inhibition of IKK represents a potential therapeutic strategy for colorectal cancer.

More Related Videos

Stimulation of Notch Signaling in Mouse Osteoclast Precursors08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Related Concept Videos

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...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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 heterodimer of NF-κB...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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...