Altered E-cadherin/β-catenin expression in feline cutaneous squamous cell carcinomas

Cutaneous squamous cell carcinoma (CSCC) continues to be the most common malignant skin tumour in cats [[1], [2], [3]]. The nature of the molecular mechanisms involved in this tumour type is poorly understood, thus limiting our ability to identify molecular markers of diagnostic and prognostic value as well as novel therapeutic targets for the treatment of feline CSCC.

Included among the molecular mechanisms altered in human CSCC progression is loss of adherens junction proteins such as E-cadherin and β-catenin [[4], [5], [6]]. Similarly, loss of membrane expression of these adhesion molecules has also been identified in CSCC progression in dogs. Furthermore, altered expression of E-cadherin and β-catenin may play a central role in canine CSCC due not only to disruption of the intercellular adherens junctions but also to dysregulated activity of the signalling pathways in which these molecules are involved [7,8].

E-cadherin is a transmembrane glycoprotein that mediates adherens intercellular junctions. The E-cadherin extracellular domain interacts with cadherins in neighbouring cells, while its cytoplasmic domain interacts with proteins such as β-catenin, which connects cadherins with the cytoskeletal network. β-catenin plays a key role in the adherens intercellular junctions and also the canonical Wnt signalling pathway. In the absence of Wnt signalling, β-catenin saturates the complex in which it takes part in the adherens junctions, whereas free cytoplasmic β-catenin is targeted for degradation by a multiprotein destruction complex. Activation of the Wnt signalling pathway turns off β-catenin destruction and the resulting stabilized β-catenin translocates to the nucleus, where it promotes expression of genes involved in cell proliferation and survival [9]. Enhanced activity of the β-catenin signalling pathway, characterized by its nuclear localization, may result from disruption of E-cadherin/β-catenin interactions at the adherens junctions and/or overactivity of the Wnt signalling pathway [10]. Although dysregulated expression of E-cadherin and β-catenin has been identified in oral squamous cell carcinomas (OSCCs) in cats [11,12], expression of these molecules in feline CSCC is still unknown.

This study aimed to explore the immunohistochemical expression pattern of E-cadherin and β-catenin in feline samples of CSCC by using a tissue microarray to elucidate whether the expression of these molecules is dysregulated in feline CSCC.

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