| Literature DB >> 30849480 |
Zhongyi Fan1, Jingjing Duan2, Lingxiong Wang1, Saisong Xiao3, Lingling Li2, Xiang Yan1, Wei Yao1, Liangliang Wu1, Sujie Zhang1, Yong Zhang1, Ye Li1, Xiang Zhu4, Yi Hu1, Dong Zhang5, Shunchang Jiao6, Xiaojie Xu7.
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.Entities:
Keywords: CSCs; FAK; HCC; Methylation; Sorafenib resistance
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Year: 2019 PMID： 30849480 DOI： 10.1016/j.canlet.2019.02.040
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679