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A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion
Longchuan Bai1, Juanita L Merchant
1Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Abstract:
A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer.
Insights
The coactivator CITED2 impacts colon cancer cell invasion and growth. Its regulation by histone deacetylase (HDAC) inhibitors suggests CITED2 as a potential therapeutic target for colon cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Histone acetyltransferase CBP/p300 regulates gene expression and cell growth, crucial for developing HDAC inhibitor strategies.
- Understanding these mechanisms is key for effective colon cancer prevention and therapy.
Purpose of the Study:
- To investigate the role of CITED2 in colon cancer.
- To explore CITED2 as a potential target for HDAC inhibitor-based interventions.
Main Methods:
- Knockdown of CITED2 in colon cancer cells.
- Gene expression profiling to analyze MMP-13 induction.
- Treatment with butyrate (HDAC inhibitor) in RKO cells.
- Ectopic expression of CITED2.
Main Results:
- CITED2 knockdown increased colon cancer cell invasiveness and MMP-13 expression.
- Butyrate upregulated CITED2 and downregulated MMP-13 in RKO cells.
- Ectopic CITED2 expression inhibited RKO cell growth.
Conclusions:
- CITED2 plays a significant role in regulating colon cancer invasion and cell growth.
- CITED2 is a potential therapeutic target for HDAC inhibitor-based colon cancer treatments.
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