ADAMTS8 is frequently down-regulated in colorectal cancer and functions as a tumor suppressor

Abstract

Colorectal cancer (CRC) is known for being a great threat to human health due to its high incidence and mortality. ADAMTS8 that belongs to the zinc metalloproteinases family acts as a tumor suppressor and is silenced by CpG methylation in several carcinomas through previous studies, but its functions in CRC remain unknown. In this report, we analyzed its expression in CRC cell lines and primary CRC tumor tissues. The results showed that ADAMTS8 was significantly down-regulated in CRC cell lines and primary tumor tissues and its expression was restored in Lovo cell lines with treatment DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine and TSA. Over-expression of ADAMTS8 in HCT116 and HT-29 resulted in inhibited cell proliferation and induced apoptosis. We also observed that ADAMTS8 suppressed cell invasion and migration. In addition, ADAMTS8 induced cell cycle arrest in G2/M phase. Furthermore, we found that ADAMTS8 led to the decrease of BCL-XL, phospho-GSK3β, β-catenin and c-myc as well as increase of cleaved caspase-9, Bax and PARP. Our findings suggest that ADAMTS8 may be considered as a functional tumor suppressor gene in CRC and has the potential to be developed as a valuable biomarker.