Cancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity. PrPc(+)CD44(+) colorectal cancer stem cells displayed high liver metastatic capability, unlike PrPc(-)CD44(+) stem cells, that was inhibited by RNAi-mediated attenuation of PrPc. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in mouse models of orthotopic metastasis. PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Our findings reveal the function of PrPc in regulating EMT in cancer stem cells, and they identify PrPc as candidate therapeutic target in metastatic colorectal cancer. Cancer Res; 73(8); 2682-94. (C)2013 AACR.
基金：
initiative of stem cell and regenerative medicine from Chinese Academy of Sciences [XDA01040409]; Ministry of Science and Technology (MOST) of China [2009CB512800, 2010CB912204]; National Natural Science Foundation of China (NSFC) [81130045, 31000614]; MOST [2010CB912204, 2010CB529403]; Institut National de la Sante et de la Recherche Medicale, Partenariat Hubert Curien - Programme Francais de Cooperation avec la Chine, Fondation Franco-Chinoise pour la Science et ses Applications
第一作者单位：[1]Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China
通讯作者：
通讯机构：[1]Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China[3]Nankai Univ, Coll Life Sci, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China[*1]Chinese Acad Sci, Inst Zool, 1 Beichen West Rd, Beijing 100101, Peoples R China
推荐引用方式(GB/T 7714)：
Du Lei,Rao Guanhua,Wang Hongyi,et al.CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer[J].CANCER RESEARCH.2013,73(8):2682-2694.doi:10.1158/0008-5472.CAN-12-3759.
APA：
Du, Lei,Rao, Guanhua,Wang, Hongyi,Li, Baowei,Tian, Weili...&Chen, Quan.(2013).CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer.CANCER RESEARCH,73,(8)
MLA：
Du, Lei,et al."CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer".CANCER RESEARCH 73..8(2013):2682-2694
医学