Related Experiment Video

Updated: May 16, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration

Caterina Ierano1, Agnes Basseville, Kenneth K W To

  • 1Medical Oncology Branch, National Cancer Institute; Bethesda, MD, USA.

Cancer Biology & Therapy
|November 30, 2012
PubMed

Insights

Histone deacetylase inhibitors (HDIs) increase CXCR4 expression but block cancer cell migration by impairing CXCL12 signaling pathways. This suggests HDIs may help prevent cancer metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The stromal cell-derived factor-1α (SDF-1α)/CXCR4 axis is implicated in cancer progression.
  • Histone deacetylase inhibitors (HDIs) demonstrate antitumor properties by influencing cell migration.

Purpose of the Study:

  • To investigate the impact of specific HDIs (apicidin, vorinostat, entinostat, romidepsin) on CXCR4 expression and function in human cancer cell lines.
  • To assess the downstream effects of HDI-induced CXCR4 modulation on cell signaling and migration.

Main Methods:

  • Treatment of human cancer cell lines (UOK121, H460, SF295, MCF7, SW620) with various HDIs.
  • Quantification of CXCR4 mRNA expression via RT-qPCR.
  • Analysis of signaling pathway activation (ERK1/2, STAT3, c-SRC) using Western blotting.
  • Assessment of cell migration assays in response to CXCL12 stimulation.

Main Results:

  • HDIs significantly upregulated CXCR4 mRNA expression in renal, non-small cell lung, and glioma cancer cells, but not in breast or colon cancer cells.
  • HDIs modulated signaling pathways, increasing pERK1/2 while decreasing pSTAT-3 and pSRC.
  • Subsequent CXCL12 stimulation showed maintained pERK1/2 but impaired STAT3 and SRC phosphorylation.
  • Both basal and CXCL12-mediated cell migration were reduced following HDI treatment.

Conclusions:

  • HDIs upregulate CXCR4 mRNA expression in specific cancer types.
  • HDIs disrupt CXCL12-mediated signaling cascades involving STAT3 and c-SRC.
  • These findings suggest a potential therapeutic role for HDIs in inhibiting cancer metastasis.
Keywords:
CXCL12CXCR4histone deacetylase inhibitormigrationromidepsin

More Related Videos

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 406:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production08:22

Retroviral Overexpression of CXCR4 on Murine B-1a Cells and Adoptive Transfer for Targeted B-1a Cell Migration to the Bone Marrow and IgM Production

Published on: May 31, 2020

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Chemotaxis and Direction of Cell Migration01:21

Chemotaxis and Direction of Cell Migration

Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon towards...
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...
X-Inactivation01:58

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.