Contactin-1 (CNTN1), also known as F3/Contactin a cell adhesion molecule, is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein involved in neuronal development, synaptic maintenance and organization of neuronal networks. CNTNs are a subpopulation of molecules belonging to the immunoglobulin (Ig) superfamily, which includes six members: CNTN1, TAG-1/CNTN2, BIG-1/CNTN3, BIG-2/CNTN4, NB-2/CNTN5 and NB-3/CNTN6^1,2.

In mammals, contactin-1 is mostly localized in the peripheral and central neural system. It is highly expressed at the axonal level and mediates various functions in both glial and neuronal cells; it is involved in neuronal and glial development and differentiation, myelination, synaptogenesis and synaptic function¹.

Contactin-1 expression profile differs in various brain regions and, within each area, it changes depending upon the cell type. For example, in the cerebellar cortex contactin-1 is predominant in granule cells in earlier developmental stages, whereas its activation is delayed in Purkinje neurons. In the hippocampus, it is detected on pyramidal neurons of CA1-CA3 fields and in granule layers of Dentate Gyrus (DG) where its expression persists in postnatally developed neurons. Hippocampal contactin-1 is highly expressed in the developing hippocampus, it progressively increases during postnatal life, but it declines during aging, paralleling cognitive impairment. This suggests that contactin-1 might play a role in memory processes, in line with studies indicating its involvement in neurotransmitter release and some forms of plasticity¹.

The role of contactin-1 in neurotransmitter release has been linked with its capability to regulate synaptic vesicle exocytosis. Contactin-1 overexpression had been shown to induce an increase of cAMP-Responsive Element Binding (CREB) phosphorylation, enhanced hippocampal-dependent LTP and memory especially in 12-months-old mice, where neurogenesis is particularly evident. Also, contactin-1 overexpression counteracts apoptosis, and induces an increase of the antiapoptotic- and neuroplasticity-pathway BDNF/CREB/Bcl-2^1,3.

Contactin-1 plays an important role in cancer progression. The expression of contactin-1 is upregulated in primary lesions, and its expression level correlates with tumor metastasis in cancer patients. Studies have demonstrated that contactin-1 also plays a key role in diseases not related to the nervous system, and its most notable function is its participation in cancer progression; in cancers such as esophageal squamous cell carcinoma (ESCC), GC, lung adenocarcinoma, oral squamous cell carcinoma (OSCC), hepatocellular carcinoma and prostate cancer^2,3.