SDC4 is a novel target of the KLF5 transcription factor

SDC4 is a member of the syndecan protein family, and its expression is upregulated in various cancers, including gastrointestinal adenocarcinomas. Although SDC4 is reportedly associated with poor prognosis, tumor growth, and metastasis, the regulatory mechanism of SDC4 gene expression in cancer cells is poorly understood. In the present study, we performed database analysis and found that the SDC4 promoter region includes several potential binding sites for the KLF5 transcription factor. Promoter assay in colorectal cancer cell line further demonstrated that two potential KLF5 protein-binding regions located near positions -70 to -40 on the SDC4 promoter are particularly critical for promoter activity. ChIP-qPCR analysis confirmed that KLF5 protein bound to this region, suggesting strong involvement of KLF5 protein. Additionally, immunohistochemical staining of human tissues revealed that SDC4 and KLF5 exhibited similar expression patterns in some colorectal cancer cases, and detected a significant positive correlation between SDC4 and KLF5 expressions. Overall, these results suggest that SDC4 expression is regulated by KLF5 at the colorectal cancer tissue level, and in cultured cell lines. In conclusion, we have newly identified SDC4 as a target gene of the KLF5 transcription factor.