Neural cell adhesion protein CNTN1 promotes the metastatic progression of prostate cancer
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels une protéine d'adhésion cellulaire (CNTN1) favorise la progression d'un cancer de la prostate et le processus métastatique
Prostate cancer (PC) metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying PC metastasis is critical for effective therapeutic intervention. In this study, we performed gene expression profiling of PC stem-like cells (PCSCs) derived from DU145 human PC cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a PC-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced PC cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. Additionally, 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 PC cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with PC progression and worse biochemical recurrence-free survival following radical prostatectomy (p<0.05). Collectively, our findings demonstrate that CNTN1 promotes PC progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.
Cancer Research 2016