title: Cellular prion protein accelerates colorectal cancer metastasis via             the Fyn-SP1-SATB1 axis.
abstract: The cellular prion protein (PrPc) is a glycoprotein anchored by glycosylphosphatidylinositol             to the cell surface and is abundantly expressed in various tissues. The putative             roles of PrPc are thought to be related to cell signaling, survival, and differentiation             and cancer progression. In this study, we demonstrated that the expression of             PrPc correlates with a more aggressive and histologically unfavorable disease             in colorectal carcinomas. Moreover, we found that PrPc mediates the process of             epithelial-mesenchymal transition and, thereby, promotes CRC metastasis. Transcriptome             profiling of PrPc-depleted cells revealed downregulation of the special AT-rich             sequence-binding protein-1 (SATB1). PrPc is demonstrated to be involved in regulating             SATB1 expression via the Fyn-SP1 pathway. Since SATB1 has been previously proposed             as a key protein that controls tumor development and progression, knockdown of             PrPc resulted in a reduced metastatic capacity in CRC cells, as well as a reduction             in distant metastases in vivo. In conclusion, our data characterize a novel molecular             mechanism that links PrPc expression to the regulation of CRC metastasis. Targeting             PrPc will, therefore, be a promising strategy to overcome the metastatic advantage             in colorectal tumors.
authors.affiliation: Department of Surgery, Huashan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Qianwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Jianming
authors.initials: J
authors.lastname: Qian
authors.forename: Fangrui
authors.initials: F
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ma
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D008565:Membrane Proteins; D018621:PrPC Proteins; C076189:SATB1 protein, human; D016329:Sp1 Transcription Factor; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn