title: Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer.
abstract: Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P < 0.05). Collectively, our findings demonstrate that CNTN1 promotes prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Judy
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Ojo
authors.affiliation: Department of Surgery, McMaster University, Hamilton, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Xiaozeng
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Surgery, McMaster University, Hamilton, Canada.
authors.forename: Jehonathan H
authors.initials: JH
authors.lastname: Pinthus
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Tariq
authors.initials: T
authors.lastname: Aziz
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Bismar
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada. The Genetics Laboratory, Institute of Women and Children's Health, Longgang District, Shenzhen, China.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wong
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: De Melo
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.affiliation: Department of Oncology, McMaster University, Hamilton, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Major
authors.affiliation: Department of Veterinary Pathology, University of Guelph, Guelph, Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Wood
authors.affiliation: Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Canada.
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Canada. damut@mcmaster.ca.
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058967:Contactin 1 / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D059467:Transcriptome / Q000235:genetics
chemical_list: C548669:CNTN1 protein, human; D015820:Cadherins; D058967:Contactin 1; D019006:Neural Cell Adhesion Molecules; D051057:Proto-Oncogene Proteins c-akt