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MX 2 is a novel regulator of cell cycle in melanoma cells

Lookup NU author(s): Dr Jérémie Nsengimana

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons LtdMX2 protein is a dynamin-like GTPase2 that has recently been identified as an interferon-induced restriction factor of HIV-1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome-wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context-dependent.


Publication metadata

Author(s): Juraleviciute M, Pozniak J, Nsengimana J, Harland M, Randerson-Moor J, Wernhoff P, Bassarova A, Oy GF, Troen G, Florenes VA, Bishop DT, Herlyn M, Newton-Bishop J, Slipicevic A

Publication type: Article

Publication status: Published

Journal: Pigment Cell and Melanoma Research

Year: 2020

Volume: 33

Issue: 3

Pages: 446-457

Online publication date: 29/10/2019

Acceptance date: 18/10/2019

Date deposited: 11/06/2020

ISSN (print): 1755-1471

ISSN (electronic): 1755-148X

Publisher: Blackwell Publishing Ltd

URL: https://doi.org/10.1111/pcmr.12837

DOI: 10.1111/pcmr.12837

PubMed id: 31660681


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