Upregulation of CPE promotes cell proliferation and tumorigenicity in colorectal cancer
- Equal contributors
1 Department of Gastroenterology, Zengcheng People’s Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng 511300, China
2 Central Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, China
3 Department of General Surgery, Zengcheng People’s Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng 511300, China
4 School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
5 Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
6 Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou 510120, China
7 Department of Clinical Laboratory, Zengcheng People’s Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng 511300, China
BMC Cancer 2013, 13:412 doi:10.1186/1471-2407-13-412Published: 5 September 2013
Colorectal 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.
In 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.
Our 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.
Taken 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.