Abstract
Cancers are among the difficult-to-treat diseases despite advances in diagnosis and treatment. Although newer effective targets remain to be discovered, targeted therapy has emerged as a promising field. In the last decade, contactin 1 (CNTN1) has surfaced as an important cancer-related molecule. CNTN1 is a neuronal membrane glycoprotein, which, if overexpressed, is found in different cancer cell lines, cancer tissues, and transgenic mice. It is positively associated with lymphatic invasion, metastasis, late TNM stage, and a short overall survival time. However, the role of CNTN1 in cancer cell proliferation remains unclear. In addition, CNTN1 is involved in cancer cell invasion, migration, metastasis, and chemoresistance by promoting epithelial-mesenchymal transition and mediating several signal transduction pathways. Several studies suggest CNTN1 as a new therapeutic target for cancers. This review aims to summarize the research developments on CNTN1 in various cancers, to establish its role in epithelial-mesenchymal transition and signal transduction pathways, and to identify promising areas for further investigation.
Highlights
Cancer remains a persistent health problem in society, and targeted therapy is an effective measure for treatment
Contactin 1 (CNTN1) is associated with several signal transduction pathways, such as the phosphatidylinositol 3-kinase (PI3K)/AKT, vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3), a7 nicotinic acetylcholine receptor/extracellular signal-regulated kinase (ERK), member A of the Ras homolog gene family (RhoA), Src-p38 mitogen-activated protein kinase (MAPK)-CCAAT/enhancerbinding protein (C/EBP) a, Notch1, and Ret protooncogene and Ret-activating protein ELE1 (RET/PTC3)
Apart from the PI3K/AKT pathway, CNTN1 is associated with the RhoA pathway in gastric cancer; VEGF-C/VEGFR-3 pathway in lung, gastric, and esophageal cancers, and oral squamous cell carcinoma (OSCC); a7 nicotinic acetylcholine receptor (nAChR)/ERK and Src-p38 MAPK-C/EBPa pathways in lung cancer; and Notch1 and RET/PTC3 pathways in thyroid cancer
Summary
Cancer remains a persistent health problem in society, and targeted therapy is an effective measure for treatment. In the immunohistochemical analysis of specimens from gastric cancer, lung adenocarcinoma, primary OSCC, prostate cancer, and esophageal cancer, CNTN1 expression was significantly positively associated with lymphatic invasion, metastasis, late TNM stage, and a short overall survival time [9, 12, 13, 16, 18, 22,23,24,25]. It was not associated with vascular or serosa invasion. NNK directly increased the expression of CNTN1, at both the TABLE 1 | Correlations between CNTN1 and other molecules in different cancers
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