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Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex
Vita M Golubovskaya1, Baotran Ho2, Jeffrey Conroy3
1Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Vita.Golubovskaya@roswellpark.org.
Cancers
|January 24, 2014
Summary
Roslin 2 (R2) compound disrupts Focal Adhesion Kinase (FAK) and p53, activating p53 and blocking tumor growth. Combining R2 with other drugs targeting FAK, Mdm-2, and p53 shows promise for colon cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Focal Adhesion Kinase (FAK) is crucial for cellular processes including proliferation, invasion, and metastasis.
- The compound Roslin 2 (R2) has demonstrated the ability to disrupt FAK and p53 interactions, activate p53, and inhibit tumor growth.
Purpose of the Study:
- To investigate the gene expression profile of R2-treated colon cancer cells.
- To evaluate the therapeutic potential of combining R2 with other agents targeting FAK, Mdm-2, and p53.
Main Methods:
- Microarray gene expression analysis was performed on R2-treated HCT116 p53+/+ and p53-/- cells.
- Gene expression changes were analyzed to identify R2-responsive genes in a p53-dependent manner.
- Combinatorial drug treatments were assessed for their effect on colon cancer cell clonogenicity.
Main Results:
- R2 treatment significantly altered the expression of 1484 genes in HCT116 p53+/+ cells, including key p53 targets like Mdm-2, Noxa-1, and RIP1.
- Down-regulated genes included Met, PLK2, KIF14, and BIRC2.
- Combined treatment with R2 and M13 or Nutlin-1 compounds synergistically reduced colon cancer cell clonogenicity in a p53-dependent manner.
Conclusions:
- R2 treatment induces a distinct gene expression profile in colon cancer cells, mediated by p53.
- Combination therapies targeting FAK, Mdm-2, and p53 represent a promising novel therapeutic strategy for colon cancer.
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