Upregulation of contactin‑1 expression promotes prostate cancer progression

Abstract

Contactin-1 (CNTN-1) has been reported to serve an oncogenic role in several cancer types. However, detailed mechanisms describing the influence of CNTN-1 in prostate cancer progression have not yet been elucidated. The present study aimed to determine the clinical significance of CNTN-1 expression in prostate cancer progression, and also to investigate the regulatory role of CNTN-1 in the proliferation, migration and invasive ability of prostate cancer cells. The results of the present study indicated that expression levels of CNTN-1 were significantly higher in prostate cancer tissues compared with adjacent normal tissues. Moreover, a high expression level of CNTN-1 was positively correlated with tumor size, stage and metastasis, as well as a poorer prognosis in patients with prostate cancer. Furthermore, CNTN-1-knockdown in prostate cancer cells (using short hairpin RNA) resulted in the significant inhibition of cancer cell proliferation, colony formation, migration and invasiveness. Silencing of CNTN-1 expression also suppressed epithelial-mesenchymal transition in prostate cancer cells via the upregulation of E-cadherin, and the downregulation of N-cadherin and vimentin expression. Inhibition of CNTN-1 expression also reduced the activity of the PI3K/AKT signaling pathway in prostate cancer cells. Thus, it was demonstrated that CNTN-1 expression is upregulated, and plays an oncogenic role, in prostate cancer cells. The results of the current study suggest that CNTN-1 may represent a promising therapeutic target, potentially improving the treatment of patients with prostate cancer.

Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

“…We provide the first demonstration of CNTN1 upregulation in CRPC in vivo ( Figure 6 ), which extends the reported CNTN1 oncogenic functions in PC [ 34 , 35 ]. This observation was further supported by the enrichment of a gene set facilitating breast cancer resistance to endocrine therapy ( Figure 2 A).…”

“…Importantly, CNTN1 promotes PC metastasis [34]. CNTN1-facilitated PC progression was also observed by others [35]. Despite a complex relationship between CNTN1 and the LE genes, our analyses nonetheless clearly reveal the novel and robust prognostic biomarker potentials of LE genes not only in PC but also in other cancer types.…”

“…Functionally, CNTN1 promotes PC metastasis [ 34 ]. Clinically, CNTN1 is associated with PC relapse [ 34 , 35 ]. Nonetheless, CNTN1 is a relatively new oncogenic protein, particularly in PC; its contributions to PC progression remain largely uncharacterized.…”

Contactin 1: An Important and Emerging Oncogenic Protein Promoting Cancer Progression and Metastasis

“…Moreover, CNTN1 was identified as a direct downstream molecule of the vascular endothelial growth factor C (VEGFC)-VEGF receptor 3 (VEFGR3)/fms-related tyrosine kinase 4 (Flt4) axis important in lymphangiogenesis and lymphatic invasion in cancers [ 53 , 54 , 55 ]. With growing interest in the investigation of CNTN1 for its cancer related functions, CNTN1 expression was found to be upregulated in many cancers including lung [ 56 , 57 , 58 , 59 ], gastric [ 60 , 61 ], breast [ 62 ], prostate [ 63 , 64 ], stomach [ 65 ], thyroid [ 7 ], esophageal [ 66 ] cancers, hepatocellular carcinoma [ 67 , 68 ], astrocytic gliomas [ 69 ], esophageal squamous cell carcinoma (ESCC) [ 70 ], and oral squamous cell carcinoma (OSCC) [ 71 ]. Unsurprisingly, increased CNTN1 expression was found to have functional associations in promoting cancer cell progression and metastasis.…”

“…The involvement of CNTN1 in cancer formation and progression is supported by its common amplification in cancers and the association of this upregulation with the clinical features of cancers. The expression level of CNTN1 showed a clear association with clinicopathological parameters and poor prognosis in many cancers including lung [ 58 ], gastric [ 60 ], prostate [ 63 ], astrocytic gliomas [ 69 ], stomach [ 65 ], thyroid [ 7 ] cancers, hepatocellular carcinoma (HCC) [ 68 ] and oral squamous cell carcinoma (OSCC) [ 54 ]. As well, CNTN1 was discovered to be a novel biomarker for melanoma [ 106 ], glioblastoma [ 112 ], and colorectal cancer [ 113 ].…”