Osteopontin promotes hepatocellular carcinoma progression via the PI3K/AKT/Twist signaling pathway

Abstract

The epithelial-mesenchymal transition (EMT) serves critical roles in the migration, invasion and metastasis of human cancer cells. This process is initiated by regulation of E-cadherin expression by the major inducers of EMT. Previous studies reported that osteopontin (OPN) is essential for hepatocellular carcinoma (HCC) metastasis as it facilitates the EMT in HCC. However, the role and clinical significance of OPN as an EMT regulator in HCC remains unknown. The present study revealed that OPN regulated the expression of Twist by activating RAC serine/threonine-protein kinase (Akt), a critical EMT regulator. Interfering with the phosphoinositide 3-kinase (PI3K)/Akt pathway may suppress the expression of Twist enhanced by OPN. Increased Twist levels in HCC were associated with poor survival and tumor recurrence in patients with HCC following surgery. A significant association was observed between OPN expression and Twist levels in HCC, and a combination of these two parameters was revealed to be a more powerful predictor of poor patient prognosis. The findings of the present study indicate that Twist serves an notable role in OPN-mediated metastasis of HCC through activation of the PI3K/Akt pathway. Twist may be a potential therapeutic target for the prevention of HCC metastasis in patients exhibiting high OPN expression.