Abstract
Cancer metastasis is a significant challenge in colorectal cancer (CRC) therapy. SET and MYND domain-containing protein 2 (SMYD2) is highly expressed in multiple cancers but is rarely studied in CRC. This study aims to identify whether abnormal expression of SMYD2 is associated with cancer metastasis in CRC. In this study, we demonstrated that SMYD2 not only promoted cell proliferation but also increased the metastatic ability of CRC. The expression of adenomatous polyposis coli 2 (APC2), an inhibitor of the Wnt/β-catenin pathway, was suppressed by SMYD2 overexpression. Overexpression of SMYD2 activated the Wnt/β-catenin pathway and then induced the epithelial-mesenchymal transition (EMT) program in CRC. Mechanistically, low APC2 expression in CRC cells was due to SMYD2-mediated DNA methylation modification. This modification might require synergism with DNMT1. In summary, our study provides new insights into SMYD2-related transcriptional regulation patterns and indicates that SMYD2 could be a potential therapeutic target for CRC patients.