Related Experiment Video

Updated: Jun 23, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB

L Kashima1, M Toyota, H Mita

  • 1Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University, Hokkaido, Sapporo, Japan.

Oncogene
|May 19, 2009
PubMed

Insights

The tumor suppressor CHFR (checkpoint with forkhead and ring finger domains) silences the NF-kappaB pathway, reducing IL-8 expression and suppressing cancer cell migration and angiogenesis.

Area of Science:

  • Molecular biology
  • Cancer research
  • Epigenetics

Background:

  • The CHFR (checkpoint with forkhead and ring finger domains) gene is silenced in various human cancers via promoter hypermethylation, indicating its role as a tumor suppressor.
  • The nuclear factor-kappaB (NF-kappaB) signaling pathway is crucial in cancer development and progression, regulating inflammation and angiogenesis.

Purpose of the Study:

  • To elucidate the function of CHFR in regulating the NF-kappaB pathway.
  • To investigate the impact of CHFR on downstream targets like IL-8 and cellular processes such as endothelial cell migration and neovascularization.

Main Methods:

  • Reporter assays to assess NF-kappaB activity.
  • CHFR knockdown and expression studies.
  • Co-immunoprecipitation to detect protein interactions.
  • Electrophoretic mobility shift assays (EMSAs) and ELISA-based binding assays.
  • In vitro endothelial cell migration assays.
  • In vivo xenograft models with adenovirus-mediated CHFR transfer.

Main Results:

  • CHFR acts as a negative regulator of the NF-kappaB pathway, independent of its RING finger domain.
  • CHFR physically interacts with p65 and inhibits its transcriptional activity, leading to downregulation of IL-8.
  • CHFR expression suppresses human endothelial cell migration and neovascularization in vivo.

Conclusions:

  • CHFR inhibits NF-kappaB signaling, thereby reducing IL-8 expression, inflammation, and angiogenesis.
  • These findings reveal a link between epigenetic silencing of CHFR, inflammation, and angiogenesis in cancer.
  • CHFR represents a potential therapeutic target for cancer intervention.

More Related Videos

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Related Concept Videos

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...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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...