ANKRD17 induces pro-survival signaling pathways that enhance cellular invasion and migration during hepatocellular carcinoma tumorigenesis

Metastasis is the primary cause of high mortality in patients with hepatocellular carcinoma (HCC) . A prior study identified ankyrin repeat domain 17 (<i>Ankrd17</i>) as a key gene linked to HCC metastasis. Through reverse genetics, it was observed that mouse liver tumors overexpressing <i>ANKRD17</i> exhibited a higher tumor load and increased expression of endothelial-mesenchymal transition (EMT) markers. Similarly, <i>ANKRD17</i> overexpression in human liver cell lines resulted in an amplified cellular motility and invasion capability, whereas knockdown studies reversed this effect. Abnormal regulation of signaling pathways was linked to increased metastasis and survival in cells overexpressing <i>ANKRD17</i>. Notably, the pro-metastatic discoidin domain receptor tyrosine kinase 1 (<i>DDR1</i>) gene was upregulated in these cells, and its suppression reduced motility and invasion without affecting AKT signaling. Clinically, higher <i>ANKRD17</i> expression correlated with aggressive HCC progression. These findings suggest that <i>ANKRD17</i> enhances metastatic progression in HCC by activating pro-metastatic and pro-survival pathways.