Elevated CREPT Expression Enhances the Progression of Salivary Gland Adenoid Cystic Carcinoma

Abstract

The elevated expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT) is reported to promote the growth of several tumors by enhancing Wnt/β-catenin signaling and cell cycle. However, the relevance of CREPT to the malignancy of salivary gland adenoid cystic carcinoma (SACC) remains unclear. The samples from 51 SACC patients were exploited in this study. We found that SACC samples exhibited a noticeably robuster CREPT expression than the para-cancerous tissues. Statistical analysis suggested that CREPT expression was significantly correlated with the T classification of SACC. To up- or down-regulating CREPT expression, the specific shRNA or full length of CREPT was delivered into SACC cell lines to examine the cell proliferation, migration, colony formation and implanted xenograft survival. Western blot assay and immunohistochemistry were applied to evaluate the expression of CREPT, cyclin D1, c-Myc and CDK4. Up-regulated CREPT in the low metastatic SACC line significantly promoted proliferation and colony formation, as well as cyclin D1, c-Myc and CDK4 expression. While knocking down of CREPT in the high metastatic SACC line remarkably reduced above effects. Furthermore, the SACC xenograft in mice confirmed that down-regulation of CREPT inhibited the in vivo tumor growth. Our study indicated that the elevated CREPT expression promoted the cell proliferation and tumor size of SACC by enhancing the expression of cyclin D1, c-Myc and CDK4, suggesting that CREPT contributed to SACC progression by stimulating cell proliferation, and might act as a potential target in future SACC therapy.