Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion.

Autor:	Elsheikh S; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK Somaia.elsheikh@nottingham.ac.uk.; Cellular Pathology Department, Nottingham University Hospitals NHS Trust, Nottingham, Nottingham, UK.; Pathology Department, Menoufia University Faculty of Medicine, Shebin El-Kom, Egypt., Kouzoukakis I; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Fielden C; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Li W; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Lashin SE; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK.; Dermatology, Menoufia University Faculty of Medicine, Shebin El-Kom, Egypt., Khair N; Histology, Menoufia University Faculty of Medicine, Shebin El-Kom, Egypt., Raposo TP; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Fadhil W; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Rudland P; School of Biological Sciences, University of Liverpool, Liverpool, UK., Aleskandarany M; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., Patel P; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK., El-Tanani M; School of Chemistry and Biosciences, University of Bradford, Bradford, West Yorkshire, UK., Ilyas M; Division of Cancer and Stem Cell, University of Nottingham, Nottingham, UK.
Jazyk:	angličtina
Zdroj:	Journal of clinical pathology [J Clin Pathol] 2022 Jan; Vol. 75 (1), pp. 24-29. Date of Electronic Publication: 2020 Nov 24.
DOI:	10.1136/jclinpath-2020-206871
Abstrakt:	Aims: Ran GTPase is involved in nucleocytoplasmic shuttling of proteins and is overexpressed in several cancers. The expression of Ran in malignant melanoma (MM) and its functional activity have not been described and were investigated in this study. Methods: The prognostic value of Ran expression was tested in a series of 185 primary cutaneous MM cases using immunohistochemistry. The functional activity of Ran was investigated in the two melanoma cell lines. Ran expression was knocked down using two siRNAs and the effect on the expression of the c-Met oncogene, a potential downstream target of Ran, was tested. Functional effects of Ran knockdown on cell motility and cell proliferation were also assessed. Results: Positive Ran expression was seen in 12.4% of MM and was associated with advanced clinical stage and greater Breslow thickness. Positive expression was an independent marker of shorter overall survival (p=0.023). Knockdown of Ran results in decreased expression of c-Met and the downstream c-met signalling targets ERK1/2. There was a significant reduction in cell migration (p<0.001) and cell invasion (p<0.001). c-Met knockdown decreased the expression of Ran through MAPK and PI3K-AKT in A375 cell line, inhibited the cell viability and migration of both A375 and G361 melanoma cell lines while invasion was enhanced. Conclusion: Ran is a poor prognostic marker in cutaneous MM. It upregulates expression of the oncogene c-Met and, possibly through this, it promotes cell motility which may in turn promote metastasis. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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