TY - JOUR
T1 - CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer
AU - Du, Lei
AU - Rao, Guanhua
AU - Wang, Hongyi
AU - Li, Baowei
AU - Tian, Weili
AU - Cui, Jiantao
AU - He, Leya
AU - Laffin, Brian
AU - Tian, Xiuyun
AU - Hao, Chunyi
AU - Liu, Hongmin
AU - Sun, Xin
AU - Zhu, Yushan
AU - Tang, Dean G.
AU - Mehrpour, Maryam
AU - Lu, Youyong
AU - Chen, Quan
PY - 2013/4/15
Y1 - 2013/4/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-12-3759
DO - 10.1158/0008-5472.CAN-12-3759
M3 - Article
C2 - 23418321
AN - SCOPUS:84876940883
SN - 0008-5472
VL - 73
SP - 2682
EP - 2694
JO - Cancer Research
JF - Cancer Research
IS - 8
ER -