Neural cell adhesion protein CNTN1 promotes the metastatic progression of prostate cancer

Judy Yan, Diane Ojo, Anil Kapoor, Xiaozeng Lin, Jehonathan H. Pinthus, Tariq Aziz, Tarek A. Bismar, Fengxiang Wei, Nicholas Wong, Jason De Melo, Jean Claude Cutz, Pierre Major, Geoffrey Wood, Hao Peng, Damu Tang

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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), aneuralcell 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.

Original languageEnglish (US)
Pages (from-to)1603-1614
Number of pages12
JournalCancer research
Volume76
Issue number6
DOIs
StatePublished - Mar 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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