Related Experiment Video

Updated: May 26, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon

Juan I Barrasa1, Nieves Olmo, Angélica Santiago-Gómez

  • 1Department of Biochemistry and Molecular Biology I, Faculty of Chemistry, Complutense University, 28040 Madrid, Spain.

Biochimica Et Biophysica Acta
|January 10, 2012
PubMed

Insights

Matrix metalloproteinase-11 (MMP-11) is upregulated in colon cancer cells by histone deacetylase inhibitors. Sp1 transcription factor and ERK1/2-MAPK signaling are crucial for this MMP-11 induction.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, is implicated in tumor progression and adverse prognosis.
  • MMP-11 expression, initially observed in tumor-surrounding stromal cells, has also been detected in macrophages and hepatocarcinoma cells.

Purpose of the Study:

  • To investigate MMP-11 expression in human colon adenocarcinoma cell lines.
  • To elucidate the regulatory mechanisms of MMP-11 gene transcription, particularly in response to histone deacetylase inhibitors.

Main Methods:

  • Analysis of MMP-11 expression in Caco-2, HT-29, and BCS-TC2 colon cancer cell lines.
  • Treatment with histone deacetylase inhibitors (butyrate and trichostatin A) to assess effects on MMP11 promoter activity and protein levels.
  • Electrophoretic mobility shift assay (EMSA), supershift assays, and chromatin immunoprecipitation to identify transcription factor binding to the MMP11 promoter.
  • Site-directed mutagenesis of Sp1 binding sites and use of mithramycin to assess Sp1's role.
  • Investigation of Smad2 and mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, JNK).

Main Results:

  • MMP-11 expression was confirmed in human epithelial colon adenocarcinoma cell lines.
  • Histone deacetylase inhibitors (butyrate and TSA) significantly increased MMP11 promoter activity and protein expression.
  • Sp1 was identified as a key transcription factor binding to the MMP11 promoter's GC-boxes, essential for basal and induced expression.
  • Regulation by histone deacetylase inhibitors involves Sp1/Smad2 heterocomplex formation, dependent on Smad acetylation.
  • ERK1/2-MAPK signaling, but not p38-MAPK or JNK, was involved in the upregulation of MMP-11 by HDAC inhibitors.

Conclusions:

  • Sp1 is a critical regulator of basal MMP-11 expression in colon cancer cells.
  • Histone deacetylase inhibitors enhance MMP-11 transcription through Sp1-mediated mechanisms involving Smad2 activation and ERK1/2-MAPK signaling.
  • These findings provide insights into the molecular regulation of MMP-11 in colon adenocarcinoma.

More Related Videos

Isolation of Primary Myofibroblasts from Mouse and Human Colon Tissue06:59

Isolation of Primary Myofibroblasts from Mouse and Human Colon Tissue

Published on: October 12, 2013

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

Related Concept Videos

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...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...