Panoply™ Human MDK Knockdown Stable Cell Line

Midkine (MDK) is a secreted heparin-binding growth factor involved in tumor progression and metastasis. Although serum MDK is widely recognized as a potential prognostic biomarker for colorectal cancer (CRC), its specific functions and underlying mechanisms in CRC development remain incompletely understood. Here, researchers demonstrate that MDK is significantly upregulated in CRC tissues and cells compared to normal counterparts. Notably, patients with high MDK expression exhibit shorter overall survival (OS). MDK overexpression promotes the invasion, migration, proliferation, and metastasis of CRC cells both in vitro and in vivo, whereas MDK knockdown reverses these effects. Mechanistic studies reveal that MDK upregulates AP2A1 expression by activating the PI3K/AKT pathway, thereby promoting epithelial-mesenchymal transition (EMT) in CRC cells. The PI3K inhibitor LY294002 significantly reduces AP2A1 levels and suppresses MDK-induced malignant behaviors. Therefore, targeting MDK-related signaling pathways may offer a novel therapeutic strategy for CRC.

Results from CCK-8, wound healing, colony formation, and EdU assays consistently demonstrated that MDK knockdown inhibited the proliferation, migration, and colony-forming capabilities of SW480 and RKO cells (Figure 1A, C, E, G), whereas MDK overexpression enhanced these phenotypes in SW620 and DLD1 cells (Figure 1B, D, F, H). Consistent with MDK's role in promoting colony formation, colony formation was reduced in MDK-knockdown SW480 and RKO cells (Figure 1E); this was further corroborated by the opposite effects observed upon MDK overexpression in SW620 and DLD1 cells (Figure 1F). Furthermore, EdU assay results showed that MDK knockdown inhibited the proliferation of SW480 and RKO cells (Figure 1G), while MDK overexpression promoted the proliferation of SW620 and DLD1 cells (Figure 1H). Collectively, these findings establish MDK as a key promoter of proliferation and migration in colorectal cancer (CRC).

Figure 1. MDK promoted CRC cell proliferation and migration. (Li T, et al., 2026)