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

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

  • Cancer Lett. 2019 May 28;450:132-143. doi: 10.1016/j.canlet.2019.02.040.
Zhongyi Fan 1,  Jingjing Duan 2,  Lingxiong Wang 1,  Saisong Xiao 3,  Lingling Li 2,  Xiang Yan 1,  Wei Yao 1,  Liangliang Wu 1,  Sujie Zhang 1,  Yong Zhang 1,  Ye Li 1,  Xiang Zhu 4,  Yi Hu 1,  Dong Zhang 5,  Shunchang Jiao 6,  Xiaojie Xu 7
Affiliations

Affiliations

  • 1 Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
  • 2 School of Medicine, Nankai University, Tianjin, China.
  • 3 Department of Anesthesia, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
  • 4 Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
  • 5 Department of Oncology, The Second Medical Centre, Chinese PLA General Hospital, Beijing, China. Electronic address: zhangdongjfjzyy@sina.com.
  • 6 Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China. Electronic address: jiaosc301@163.com.
  • 7 Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China. Electronic address: miraclexxj@126.com.
PMID: 30849480 DOI: 10.1016/j.canlet.2019.02.040
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.

Keywords

CSCs; FAK; HCC; Methylation; Sorafenib resistance.

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