PTK2 promotes cancer stem cell traits in hepatocellular carcinoma by activating Wnt/β-catenin signaling.

Abstract:

:Emerging evidence indicates that cancer stem cells (CSCs) are involved in tumorigenesis, tumor recurrence, and therapeutic resistance in hepatocellular carcinoma (HCC). However, the mechanisms underlying HCC CSC regulation remain largely unknown. Here we report our analysis of 97 paraffin-embedded HCC tumor specimens. We found that protein tyrosine kinase 2 (PTK2) expression correlated with liver CSC marker expression, overall survival, and recurrence-free survival in HCC patients. Our results further showed that PTK2 activated Wnt/β-catenin signaling by promoting nuclear accumulation of β-catenin in HCC cells. In this manner, PTK2 activates CSC traits and drives tumorigenicity in HCC cells, leading to HCC recurrence and sorafenib resistance. Moreover, PTK2 expression was negatively correlated with its level of promoter methylation. PTK2 apparently acts as an oncogene by increasing CSC traits and tumorigenicity in HCC. The present data suggest that PTK2 may be a novel prognostic biomarker for HCC recurrence, and a therapeutic target for HCC treatment.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Fan Z,Duan J,Wang L,Xiao S,Li L,Yan X,Yao W,Wu L,Zhang S,Zhang Y,Li Y,Zhu X,Hu Y,Zhang D,Jiao S,Xu X

doi

10.1016/j.canlet.2019.02.040

subject

Has Abstract

pub_date

2019-05-28 00:00:00

pages

132-143

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(19)30126-0

journal_volume

450

pub_type

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