Related Experiment Video
Updated: Aug 20, 2025
28:15
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
12.4K
Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression
Verawan Boonsanay1, Mohammed H Mosa1, Mario Looso2
1Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt am Main, Germany.
Gastroenterology
|November 19, 2022
Summary
Loss of Suv4-20h2, which controls H4K20me3, drives right-sided colorectal cancer by altering chromatin. Targeting this epigenetic mechanism offers a new therapeutic strategy for this cancer subtype.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Research
Background:
- Epithelial cell plasticity in colorectal carcinogenesis is regulated by epigenetic processes.
- SUV420H2, a lysine methyltransferase, regulates epithelial plasticity and H4K20 trimethylation (H4K20me3).
- Loss of H4K20me3 is a potential hallmark of cancer, but Suv4-20h2's role in colorectal cancer is unknown.
Purpose of the Study:
- To investigate the role of Suv4-20h2 and H4K20me3 in colorectal cancer.
- To explore the epigenetic mechanisms driving colorectal cancer tumorigenesis.
- To identify potential subtype-specific therapeutic targets for colorectal cancer.
Main Methods:
- Analysis of histone modifications in patient-derived colorectal cancer organoids.
- Genetic manipulation of organoids and xenograft models for functional studies.
- Gene expression profiling, chromatin accessibility assays (MNase), and ChIP to assess epigenetic regulation.
Main Results:
- Reduced H4K20me3 levels and increased chromatin accessibility were observed in right-sided colorectal cancer organoids.
- Inhibiting histone demethylase (methylstat) reduced tumor growth in right-sided cancer models.
- Suv4-20h2-mediated H4K20me3 is crucial for heterochromatin compaction and preventing R-loop formation.
- Gene expression analysis revealed overlapping signatures related to chromatin silencing, DNA methylation, and stemness/Wnt signaling between depleted murine organoids and right-sided colorectal cancer organoids.
Conclusions:
- Loss of Suv4-20h2-mediated H4K20me3 promotes right-sided colorectal tumorigenesis via epigenetic chromatin compaction.
- This study reveals a novel, epigenetically controlled mechanism driving a specific colorectal cancer subtype.
- Findings suggest a new subtype-specific therapeutic approach for aggressive colorectal cancer.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
5.0K
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...
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...
5.0K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.7K
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...
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...
7.7K
02:07Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K
02:23Abnormal Proliferation
4.6K
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...
4.6K