NME1 Drives Expansion of Melanoma Cells with Enhanced Tumor Growth and Metastatic Properties

Wang, Y., Leonard, M. K., Snyder, D. E., Fisher, M. L., Eckert, R. L., Kaetzel, D. M. (August 2019) NME1 Drives Expansion of Melanoma Cells with Enhanced Tumor Growth and Metastatic Properties. Mol Cancer Res, 17 (8). pp. 1665-1674. ISSN 1541-7786

URL: https://www.ncbi.nlm.nih.gov/pubmed/31123173
DOI: 10.1158/1541-7786.mcr-18-0019

Abstract

Melanoma is a lethal skin cancer prone to progression and metastasis, and resistant to therapy. Metastasis and therapy resistance of melanoma and other cancers are driven by tumor cell plasticity, largely via acquisition/loss of stem-like characteristics and transitions between epithelial and mesenchymal phenotypes (EMT/MET). NME1 is a metastasis suppressor gene that inhibits metastatic potential when its expression is enforced in melanoma and other cancers. Herein, we have unmasked a novel role for NME1 as a driver of melanoma growth distinct from its canonical function as a metastasis suppressor. NME1 promotes expansion of stem-like melanoma cells that exhibit elevated expression of stem cell markers (e.g., Sox2, Sox10, Oct-4, KLF4, and Ccnb-1), enhanced growth as melanoma spheres in culture, and enhanced tumor growth and lung colonizing activities in vivo. In contrast, NME1 expression did not affect the proliferation of melanoma cell lines in monolayer culture conditions. Silencing of NME1 expression resulted in a dramatic reduction in melanoma sphere size, and impaired tumor growth and metastatic activities of melanoma sphere cells when xenografted in immunocompromised mice. Individual cells within melanoma sphere cultures displayed a wide range of NME1 expression across multiple melanoma cell lines. Cell subpopulations with elevated NME1 expression were fast cycling and displayed enhanced expression of stem cell markers. IMPLICATIONS: Our findings suggest the current model of NME1 as a metastasis-suppressing factor requires refinement, bringing into consideration its heterogeneous expression within melanoma sphere cultures and its novel role in promoting the expansion and tumorigenicity of stem-like cells.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > melanomas
diseases & disorders > cancer > metastasis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > suppressor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL labs > Mills lab
Depositing User: Matthew Dunn
Date: August 2019
Date Deposited: 20 Aug 2019 20:47
Last Modified: 20 Aug 2019 20:47
PMCID: PMC6677611
Related URLs:
URI: http://repository.cshl.edu/id/eprint/38296

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