The Role of Contactin 1 in Cancers: What We Know So Far

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.

Epithelial–Mesenchymal Transition Signaling and Prostate Cancer Stem Cells: Emerging Biomarkers and Opportunities for Precision Therapeutics

“…Contactin1 ( Cntn -1 ) is a cell adhesion neuronal membrane glycoprotein belonging to the immunoglobulin superfamily. The protein has been shown to utilize EMT-dependent promotion for enhanced cell invasion, migration, and metastasis in several different types of carcinoma [ 43 ]. Downregulation of Cntn-1 resulted in decreased activity of the PI3K/Akt signaling and docetaxel resistance in PCa cells lines and xenografts [ 44 ].…”

Prognostic implication and immunological value of contactin 1 expression in pan‐cancer

“…The altered CNTN1 expression in the intercellular adhesive properties of cancer cells certainly plays a role in tumorigenesis. CNTN1 promotes an adhesion switch during the epithelial‐to‐mesenchymal transition that is associated with cancer invasion by elevating PI3K/AKT and NOTCH signalling pathways 53,54 . It was proved that CNTN1 acts as a downstream effector of the VEGF‐C/VEGFR3 signalling pathway in cancer cells 55 .…”

“…CNTN1 promotes an adhesion switch during the epithelial-to-mesenchymal transition that is associated with cancer invasion by elevating PI3K/AKT and NOTCH signalling pathways. 53,54 It was proved that CNTN1 acts as a downstream effector of the VEGF-C/VEGFR3 signalling pathway in cancer cells. 55 CNTN1 was also confirmed to be regulated by the Wnt signalling, Hedgehog signalling, and calcium signalling pathways by KEGG analysis.…”

CNTN-1 Upregulation Induced by Low-Dose Cisplatin Promotes Malignant Progression of Lung Adenocarcinoma Cells via Activation of Epithelial-Mesenchymal Transition

“…CNTN -1, located on chromosome 12q11-q12 and a neuronal cell adhesion molecules of the immunoglobulin superfamily, participates in nervous system development ( Su et al, 2006 ). Additionally, CNTN -1 was also reported to promote the malignant progression of cancer cells as a downstream molecule of the VEGF-C/Flt-4 axis ( Zhou et al, 2015 ; Liang et al, 2020 ). In our previous studies, CNTN -1 expression was found to be positively correlated with lymphatic invasion of lung adenocarcinoma patients who received adjuvant cisplatin- or carboplatin-based treatment after surgery ( Chen et al, 2015 ), suggesting that the CNTN -1 upregulation may be induced by platinum-based chemotherapy.…”