The Study of the Specific Proteins of Colorectal Cancer for Therapy Application

The objective of this research is to investigate the effective treatment of patients with colorectal cancer. Previously we have successfully uncovered several differentially expressed proteins in colorectal carcinoma by using gel-assisted digestion and iTRAQ labeling or label-free mass spectrophotometry. The results have revealed that 23 selected differentially expressed proteins, including stomatin-like protein 2 (SLP-2), phospholipid scramblase 1 (PLSCR 1) and transport protein Sec61 subunit beta (SEC61β), may play an important role in colorectal cancer carcinogenesis and can serve as promising diagnostic or therapeutic targets for colorectal cancer. Preliminary results have shown the therapy by targeting the activity of PLSCR1 is clearly effective against colorectal cancer both in colorectal cell line (HT29 cell line) and in a mouse model. This proposal hypothesize that the apparent dependency of colorectal cancer on one or a few specific proteins for maintenance of the malignant phenotype. To prove this hypothesis, we will evaluate the therapy efficacy of agents against the activity of specific proteins in colorectal cancer and investigate the influence of differentially expressed proteins on the signal transduction. The strategy combines the use of RNA interference, antibody against specific protein, cell proliferation assay and soft agar colony assay to identify the specific proteins that are critical for maintenance of the malignant phenotype of colorectal cancer. Once the dependency of the specific proteins for maintenance of the malignant phenotype have been identified, we will apply this mode of therapeutic approach to mouse models. The results enabled us to uncover that survival of mice with transplanted colorectal cancer can be significantly improved after a treatment by administering an antibody or siRNA against one or more of the specific proteins. Furthermore, we will also investigate the signal transduction pathway of the specific proteins in colorectal cancer carcinogenesis by treating HT29 cell line with siRNA against the specific protein. The results of this project will help us understand the dependency of specific proteins for maintenance of the malignant phenotype and develop more effective and specific forms of colorectal cancer prevention and therapy.

Project ID:PC10008-0622
External Project ID:NSC100-2320-B182-012