P-cadherin in HNSCC

P-cadherin is one of the classical cadherins, like E-cadherin and N-cadherin. Cadherins on adjacent cells establish homophilic interactions leading to selective cell adhesion. This provides a foundation for proper tissue architecture.

In recent years it became clear that cadherins are not only blunt cellular connectors but are involved in a delicately concerted signal circuitry which is responsible for cell survival, differentiation, migration and invasion.

Apart from redundant functional features cadherins exhibit specific aspects which are important during the development of malignancies. N-cadherin for instance,  expressed in carcinoma cells is associated with enhanced migration and proliferation. Only recently, the functional differences between P-cadherin and E-cadherin began to emerge and are of critical interest for our research area. In the oral epithelium these cadherins are expressed in different compartments. While E-cadherin is expressed in all cell layers, P-cadherin is confined to basal and suprabasal cell layers. This distinct localization implies specific functional influence.

Our research mainly focuses on the role of P-cadherin in oral squamous cell carcinoma. P-cadherin is responsible for the upregulation of cytokeratin 1/10 in normal oral keratinocytes facilitating differentiation of basal cells. This differentiation circuitry does not occur in  oral squamous cell carcinoma cells.

Our group and others found P-cadherin aberrantly expressed in beginning and advanced stages of oral squamous cell carcinoma. The membraneous loss of P-cadherin is associated with poor prognosis and worse overall patient survival.