Decreased expression of SCUBE2 is associated with progression and prognosis in colorectal cancer

Abstract

Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2 (SCUBE2), a member of the SCUBE protein family, is a secreted and membrane-associated multi-domain glycoprotein. SCUBE2 is known as a novel tumor suppressor and a useful prognostic marker in breast cancer. In the present study, we investigated the expression (including mRNA and protein levels) of SCUBE2 in colorectal cancer (CRC) and adjacent normal tissues, using quantitative realtime PCR, western blot analysis and immunohistochemistry on a tissue microarray. Upregulation of SCUBE2 was achieved by transient transfection in RKO cell lines, and the effects of SCUBE2 on tumor proliferation, invasion, migration and apoptosis were evaluated by a series of functional experiments. The results indicated that SCUBE2 expression was decreased at the transcriptional and translational levels in CRC tissues and significantly associated with clinical stage, the depth of tumor invasion, lymph-node metastasis, distant metastasis and histological grade. Patients with SCUBE2-positive tumors had a lower recurrence rate and better survival than patients with SCUBE2-negative tumors. Moreover, upregulation of SCUBE2 had a limited effect on cell apoptosis but significantly inhibited tumor cell proliferation, migration and invasion in vitro. In conclusion, SCUBE2 plays an important role in suppressing CRC progression and prognosis. Our findings suggested that SCUBE2 may serve as a novel tumor suppressor and a potential therapeutic target for CRC patients.