Abstract
BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood.MethodsIn the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells.ResultsOur study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1.ConclusionsTaken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death
Murthy et al reported that Carboxypeptidase E (CPE) was significantly elevated in many human cancers, and its upregulation was correlated with tumor growth and metastasis [9]
Western blot analysis and real-time qRT-PCR results showed that CPE was overexpressed in all CRC cell lines compared to primary normal colorectal epithelial cells (Figure 1A-B)
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related deaths [1]. After being packaged into secretory granules, these precursors are processed sequentially, first, by prohormone convertases (PC1/3 and PC2) to remove the carboxyl side of paired basic residues to yield basic residue-extended peptides [11,12], by a subset of soluble CPE to cleave the basic residues to generate biologically active peptide hormones and neuropeptides [10,13,14].
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