Journal
CANCER LETTERS
Volume 450, Issue -, Pages 132-143Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.02.040
Keywords
FAK; HCC; CSCs; Sorafenib resistance; Methylation
Categories
Funding
- National Natural Science Foundation of China [81702936, 81822037, 81472589, 81672602, 81402345, 81502264, 81872090]
- Natural Science Foundation of Beijing [7172199]
- Postdoctoral Science Foundation of China [2017M613389, 2018T111142]
- Logistics Scientific Research project [BWS16J010]
- Capital Foundation of Medical Developments [2016-4-5061]
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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/beta-catenin signaling by promoting nuclear accumulation of beta-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.
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