title: Cripto-1 promotes epithelial-mesenchymal transition in prostate cancer via Wnt/β-catenin signaling.
abstract: The Cripto-1 (CR-1) derived EGF-CFC family was overexpressed in tumor development enhancing proliferation, epithelial-mesenchymal transition (EMT) and migration of tumor cells. However, correlation between CR-1 and prostate cancer (PCa) remains still unclear. In the present study, we proved that CR-1 was expressed in PCa and its function was in the progression of PCa. Compared with benign prostatic hyperplasia (BPH) tissues, we confirmed that PCa tissues had high expression of CR-1 by immunohistochemistry and statistical data showed that CR-1 promoted properties of EMT in PCa tissues, including the downregulation of the cell adhesion molecules β-catenin (membrane) and E-cadherin while upregulating transcription factors β-catenin. Overexpression of CR-1 had close relationship with PSA, Gleason, clinical staging and lymph node metastasis in PCa patients. Then, we found that PC-3 cells transfected with CR-1-shRNA inhibited EMT using RT-PCR, RT-qPCR, western blotting and immunofluorescence. Also, we evaluated cell invasive ability in vitro by transwell and wound-healing assay. Our data showed that transfected CR-1-shRNA altered EMT including β-catenin, E-cadherin, c-myc, GSK-3, p-GSK and Wnt/β-catenin pathway in PC-3. It also suppressed PC-3 cell migration. Additionally, our results displayed that Licl had antitumor activity against PC-3 through the inhibition of Wnt/β-catenin pathway. Inhibition of cell viability was dose-time dependent. The present study proved that CR-1 regulates EMT of PCa by Wnt/β-catenin pathway. Hence, CR-1 may provide a new biological marker, and possibly contributes to clinical treatment against PCa.
authors.affiliation: Prostate Disease Laboratory, Tianjin Institute of Urology, Tianjin 300211, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Prostate Disease Laboratory, Tianjin Institute of Urology, Tianjin 300211, P.R. China.
authors.forename: Zhenbang
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Prostate Disease Laboratory, Tianjin Institute of Urology, Tianjin 300211, P.R. China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Yang
authors.affiliation: Prostate Disease Laboratory, Tianjin Institute of Urology, Tianjin 300211, P.R. China.
authors.forename: Ranlu
authors.initials: R
authors.lastname: Liu
authors.affiliation: Prostate Disease Laboratory, Tianjin Institute of Urology, Tianjin 300211, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C070636:TDGF1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin