AMPK promotes the survival of colorectal cancer stem cells

作     者：Bing Guo Xin Han Diane Tkach Shu-Guang Huang Dong Zhang 

作者机构：Pfizer Research Novartis Pharmaceuticals Department of Biomedical SciencesCollege of Osteopathic Medicine New York Institute of Technology 

出 版 物：《Animal Models and Experimental Medicine》 (动物模型与实验医学（英文）)

年 卷 期：2018年第1卷第2期

页      面：134-142页

学科分类：10[医学] 

主　　题：AMP-activated protein kinase cancer metabolism colorectal cancer stem cells patient-derived xenograft 

摘      要：Background: Colorectal cancer(CRC) is the third most commonly diagnosed cancer in males and the second in females worldwide in 2012. In the past 20 years, strong evidence suggests that cancer stem cells are the main culprit of cancer metastasis,chemotherapy resistance, and ***: To further understand the unique biological properties of cancer stem cells and uncover novel molecular targets to eradicate them, we first established a panel of patient-derived xenograft(PDX) tumor models using tumors surgically removed from human colorectal cancer patients. We then isolated CRC cancer stem cells based on their ALDH activity using fluorescent-activated cell sorting(FACS)and characterized their metabolic ***: Interestingly, we found that the CRC cancer stem cells(ie, CRC cells with higher ALDH activity, or ALDH+) express higher level of antioxidant genes and have lower level of reactive oxygen species(ROS) than non-CRC cancer stem cells(ie, CRC cells with lower ALDH activity, or ALDHà). The CRC cancer stem cells also possess more mitochondria mass and show higher mitochondrial activity. More intriguingly,we observed higher AMP-activated protein kinase(AMPK) activities in these CRC cancer stem cells. Inhibition of the AMPK activity using 2 AMPK inhibitors, Compound C and Iodotubercidin, preferentially induces cell death in CRC cancer stem ***: We propose that AMPK inhibitors may help to eradicate the CRC cancer stem cells and prevent the relapse of CRCs.