Nectin like-5 overexpression correlates with the malignant phenotype in cutaneous melanoma
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Valentina Bevelacqua1, Ylenia Bevelacqua2, Saverio Candido1, Evangelia Skarmoutsou1, Alfredo Amoroso1, Claudio Guarneri3, Angela Strazzanti4, Pietro Gangemi5, Maria C. Mazzarino1, Fabio D’Amico1, James A. McCubrey6, Massimo Libra1,^ and Grazia Malaponte1,*,^
1 Section of pathology and Oncology, Department of Bio-medical Sciences, University of Catania, Catania, Italy;
2 Section of Plastic Surgery, Department of Medicine and Surgery Specialities, University of Catania, Italy;
3 Section of Dermatology, Department of Social Territorial Medicine, University of Messina, Messina, Italy;
4 Department of Surgery, Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino, Catania, Italy;
5 Pathology Unit, Azienda Ospedaliero-Universitaria Vittorio Emanuele-Ferrarotto-S. Bambino, Catania, Italy;
6 Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, Greenville, NC, USA.
^ Co-last author and co-corresponding author
Massimo Libra, email:
Keywords: NECL-5, melanoma, nevus, skin
Received: August 08, 2012, Accepted: August 24, 2012, Published: August 26, 2012
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.
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