title: CD44-positive cancer stem cells expressing cellular prion protein contribute to metastatic capacity in colorectal cancer.
abstract: 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.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Lei
authors: L
authors: Du
authors: Guanhua
authors: G
authors: Rao
authors: Hongyi
authors: H
authors: Wang
authors: Baowei
authors: B
authors: Li
authors: Weili
authors: W
authors: Tian
authors: Jiantao
authors: J
authors: Cui
authors: Leya
authors: L
authors: He
authors: Brian
authors: B
authors: Laffin
authors: Xiuyun
authors: X
authors: Tian
authors: Chunyi
authors: C
authors: Hao
authors: Hongmin
authors: H
authors: Liu
authors: Xin
authors: X
authors: Sun
authors: Yushan
authors: Y
authors: Zhu
authors: Dean G
authors: DG
authors: Tang
authors: Maryam
authors: M
authors: Mehrpour
authors: Youyong
authors: Y
authors: Lu
authors: Quan
authors: Q
authors: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D018621:PrPC Proteins; D019950:Mitogen-Activated Protein Kinase 1