The Notch pathway promotes the cancer stem cell characteristics of CD90 + cells in hepatocellular carcinoma

// Jing Luo 1, 2 , Peng Wang 1 , Ronghua Wang 1 , Jinlin Wang 1 , Man Liu 1 , Si Xiong 1 , Yawen Li 1 , Bin Cheng 1 1 Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China 2 Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China Correspondence to: Bin Cheng, e-mail: b.cheng@tjh.tjmu.edu.cn Keywords: Notch pathway, HCC, CD90, cancer stem cells Received: June 02, 2015      Accepted: December 07, 2015      Published: December 19, 2015 ABSTRACT CD90 has been identified as a marker for liver cancer stem cells (CSCs) that are responsible for tumorigenic activity, but it is not known how CD90 + cells contribute to tumor initiation and progression. Our data demonstrated that high expression of CD90 in Hepatocellular Carcinoma (HCC) tissues correlated with venous filtration in HCC patients. CD90 + cells isolated from HCC cell lines exhibited increased tumorigenicity, chemoresistance, tumor invasion and metastasis. Notch pathway was activated in CD90 + cells and we found that inhibition of Notch pathway in CD90 + CSCs decreased tumorigenicity, cell invasion, migration and expression of stem cell related genes. Activation of Notch pathway in CD90 - cells induced self-renewal, invasion and migration. Furthermore, we observed that cancer stem cell features were facilitated by stimulating G1-S transition in the cell cycle phase and inhibiting apoptosis mediated by Notch pathway. Our findings suggested CD90 could be used as a potential biomarker for HCC CSCs, and that cancer stem cell activity was elevated through up activated Notch pathway in CD90 + CSCs.