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

Abstract

Even with recent progress, cancer remains the second leading cause of death, outlining a need to widen the current understanding on oncogenic factors. Accumulating evidence from recent years suggest Contactin 1 (CNTN1)’s possession of multiple oncogenic activities in a variety of cancer types. CNTN1 is a cell adhesion molecule that is dysregulated in many human carcinomas and plays important roles in cancer progression and metastases. Abnormalities in CNTN1 expression associate with cancer progression and poor prognosis. Mechanistically, CNTN1 functions in various signaling pathways frequently altered in cancer, such as the vascular endothelial growth factor C (VEGFC)-VEGF receptor 3 (VEFGR3)/fms-related tyrosine kinase 4 (Flt4) axis, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), Notch signaling pathway and epithelial-mesenchymal transition (EMT) process. These oncogenic events are resulted via interactions between tumor and stroma, which can be contributed by CNTN1, an adhesion protein. CNTN1 expression in breast cancer correlates with the expression of genes functioning in cancer-stroma interactions and skeletal system development. Evidence supports that CNTN1 promotes cancer-stromal interaction, resulting in activation of a complex network required for cancer progression and metastasis (bone metastasis for breast cancer). CNTN1 inhibitions has been proven to be effective in experimental models to reduce oncogenesis. In this paper, we will review CNTN1′s alterations in cancer, its main biochemical mechanisms and interactions with its relevant cancer pathways.

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

“…Contactin 1 (CNTN1) is an Ig-like neural cell adhesion protein [ 21 ]; it plays an important role in the central nervous system through promoting axon elongation in the cerebellum, formation of the septate-like junctions between axons and myelinating glial cells, and generation of the neuromuscular junction [ 22 , 23 , 24 ]. Recent evidence clearly reveals CNTN1-derived oncogenic actions [ 25 ]. CNTN1 facilitates lung cancer metastasis [ 26 ] and associates with poor prognosis in patients with lung, esophageal and oral squamous cell carcinomas [ 26 , 27 , 28 ], and hepatocellular carcinoma [ 29 ].…”

Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network

“…This research represents a novel attempt in improving BCR risk assessment through the angle of IQGAP1. We have approached this research because the dynamics of cytoskeleton organization is essential for tumor progression through processes of epithelial mesenchymal transition (EMT) and mesenchymal epithelial transition (MET) as well as communications with microenvironment [ 91 ]. IQGAP1 plays an important role in cytoskeleton reorganization via stabilization of the GTP-bound Cdc42 and Rac1 [ 20 ].…”

Mechanisms of Primary Membranous Nephropathy

“…CNTN1 is anchored on the cell surface and contains multiple extracellular motifs ( Figure 2 D), which share structural similarities with PLA2R and THSD7A ( Figure 2 ). CNTN1 modulates multiple cellular signaling pathways and facilitates tumorigenesis [ 171 , 172 , 173 , 174 ]. Whether CNTN1 is a novel MN antigen should be further explored.…”