PTK2 Promotes Hepatocellular Carcinoma Cancer Stem Cell Traits and Tumorigenicity by Activating Wnt/β-Catenin Signaling

Abstract

Emerging evidence has demonstrated that cancer stem cells (CSCs) are involved in tumorigenesis, tumor recurrence and therapy resistance in hepatocellular carcinoma (HCC). However, the mechanisms underlying the regulation of CSCs in HCC remain largely unknown. Here, we report that protein tyrosine kinase 2 (PTK2) expression correlates with liver CSC marker expression, overall survival and recurrence-free survival in HCC patients. PTK2 has an activating effect on Wnt/β-catenin signaling caused by PTK2 promotion of nuclear accumulation of β-catenin protein in HCC cells. PTK2 activates CSC traits and tumorigenicity of HCC cells, leading to HCC recurrence and sorafenib resistance. Moreover, PTK2 expression negatively correlates with the methylation level of its promoter. PTK2 acts as an oncogene by increasing CSC traits and tumorigenicity in HCC. Our findings suggest PTK2 as a novel prognostic biomarker for HCC recurrence and a therapeutic target for HCC treatment. Funding Statement: This work was supported by the National Natural Science Foundation of China (81702936, 81472589, 81672602, 81402345), the Natural Science Foundation of Beijing (7172199) and a General Financial Grant from the Postdoctoral Science Foundation of China (2017M613389) and Logistics Scientific Research project (BWS16J010). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The study was conducted with informed consent of the patients and with the approval of the Institutional Review Committees of the Chinese PLA General Hospital.