Abstract

NECL-5 is involved in regulating cell-cell junctions, in cooperation with cadherins, integrins and platelet-derived growth factor receptor, that are essential for intercellular communication. Its role in malignant transformation was previously described. It has been reported that transformation of melanocytes is associated with altered expression of adhesion molecules suggesting the potential involment of NECL-5 in melanoma development and prognosis. To shed light on this issue, the expression and the role of NECL-5 in melanoma tissues was investigated by bioinformatic and molecular approaches. NECL-5 was up-regulated both at the mRNA and the protein levels in WM35, M14 and A375 cell lines compared with normal melanocytes. A subsequent analysis in primary and metastatic melanoma specimens confirmed "in vitro" findings. NECL-5 overexpression was observed in 53 of 59 (89.8%) and 12 of 12 (100%), primary melanoma and melanoma metastasis, respectively; while, low expression of NECL-5 was detected in 12 of 20 (60%) benign nevi. A significant correlation of NECL-5 overexpression was observed with most of known negative melanoma prognostic factors, including lymph-node involvement (P = 0.009) and thickness (P = 0.004). Intriguingly, by analyzing the large series of melanoma samples in the Xu dataset, we identified the transcription factor YY1 among genes positively correlated with NECL-5 (r = 0.5). The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression.

Highlights

  • Cutaneous melanoma represents the most aggressive and lethal malignancy of the skin

  • Cutaneous melanoma is the example of tumor type which progresses through various stages, from benign nevi to metastatic cancer, culminating in an highly aggressive disseminating tumor [40]

  • These findings suggest its role in melanoma progression

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Summary

Introduction

Cutaneous melanoma represents the most aggressive and lethal malignancy of the skin. Despite advances in melanoma treatment [1,2,3,4], mortality from melanoma is still increasing [5]. It is well known that up- or downregulation of several adhesion molecules, such as N- and E-cadherin, MCAM (melanoma cell adhesion molecule), VCAM (vascular cell adhesion molecule), integrins, can be involved in the progression of several cancer types [12,13,14,15,16], including melanoma [17,18,19] In this context, emphasis has recently been placed on the cell adhesion molecule, nectin like molecule-5 (NECL5), named NECL-5/NECL-5/CD155/ Tage4 [20,21,22,23]. The involvement of NECL-5 in human cutaneous melanoma is still lacking Overall, these data led us to investigate if NECL-5 expression may play a role in melanoma development and progression

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