title: Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.
abstract: BACKGROUND
  Current management of patients diagnosed with prostate cancer (PCa) is very effective; however, tumor recurrence with Castrate Resistant Prostate Cancer (CRPC) and subsequent metastasis lead to poor survival outcome, suggesting that there is a dire need for novel mechanistic understanding of tumor recurrence, which would be critical for designing novel therapies. The recurrence and the metastasis of PCa are tightly linked with the biology of prostate cancer stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT) phenotype. Increasing evidence suggests that EMT-type cells share many biological characteristics with cancer stem-like cells.
  
  
  RESULTS
  In this study, we found that PCa cells with EMT phenotype displayed stem-like cell features characterized by increased expression of Sox2, Nanog, Oct4, Lin28B and/or Notch1, consistent with enhanced clonogenic and sphere (prostasphere)-forming ability and tumorigenecity in mice, which was associated with decreased expression of miR-200 and/or let-7 family. Reversal of EMT by re-expression of miR-200 inhibited prostasphere-forming ability of EMT-type cells and reduced the expression of Notch1 and Lin28B. Down-regulation of Lin28B increased let-7 expression, which was consistent with repressed self-renewal capability.
  
  
  CONCLUSIONS
  These results suggest that miR-200 played a pivotal role in linking the characteristics of cancer stem-like cells with EMT-like cell signatures in PCa. Selective elimination of cancer stem-like cells by reversing the EMT phenotype to Mesenchymal-Epithelial Transition (MET) phenotype using novel agents would be useful for the prevention of tumor recurrence especially by eliminating those cells that are the "Root Cause" of tumor development and recurrence.
authors.affiliation: Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Dejuan
authors.initials: D
authors.lastname: Kong
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Banerjee
authors.forename: Aamir
authors.initials: A
authors.lastname: Ahmad
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Li
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Seema
authors.initials: S
authors.lastname: Sethi
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology*; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C516326:LIN28B protein, human; D008222:Lymphokines; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C427493:PDGFD protein, human; C494173:POU5F1 protein, human; D010982:Platelet-Derived Growth Factor; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C487931:mirnlet7 microRNA, human
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