Publication: Mahogunin ring finger 1 is required for genomic stability and modulates the malignant phenotype of melanoma cells.
Authors
Martínez-Vicente, Idoya ; Abrisqueta, Marta ; Bennett, Dorothy C. ; Sirés-Campos, Julia ; Castejón Griñán, María ; García-Borrón Martínez, José Carlos ; Herraiz Serrano, Cecilia María ; Jiménez-Cervantes Frigols, Celia ; Olivares Sánchez, María Concepción
item.page.secondaryauthor
item.page.director
Publisher
MDPI
publication.page.editor
publication.page.department
DOI
https://doi.org/10.3390/cancers12102840
item.page.type
info:eu-repo/semantics/article
Description
© 2020 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in cancer. To access the final edited and published work see https://doi.org/10.3390/cancers12102840
Abstract
The mouse mahoganoid mutation abrogating Mahogunin Ring Finger‐1 (MGRN1) E3 ubiquitin ligase expression causes hyperpigmentation, congenital heart defects and neurodegeneration. To study the pathophysiology of MGRN1 loss, we compared Mgrn1‐knockout
melanocytes with genetically matched controls and melan‐md1 (mahoganoid) melanocytes. MGRN1 knockout induced a more differentiated and adherent phenotype, decreased motility, increased the
percentage of cells in the S phase of the cell cycle and promoted genomic instability, as shown by stronger γH2AX labelling, increased burden of DNA breaks and higher abundance of aneuploid cells. Lack of MGRN1 expression decreased the ability of melanocytes to cope with DNA breaks
generated by oxidizing agents or hydroxyurea‐induced replicative stress, suggesting a contribution of genomic instability to the mahoganoid phenotype. MGRN1 knockout in B16‐F10 melanoma cells also augmented pigmentation, increased cell adhesion to collagen, impaired 2D and 3D motility and caused genomic instability. Tumors formed by Mgrn1‐KO B16‐F10 cells had lower mitotic indices, fewer Ki67‐positive cells and showed a trend towards smaller size. In short‐term lung colonization assays Mgrn1‐KO cells showed impaired colonization potential. Moreover, lower
expression of MGRN1 is significantly associated with better survival of human melanoma patients. Therefore, MGRN1 might be an important phenotypic determinant of melanoma cells.
publication.page.subject
Citation
Cancers 2020, 12, 2840
item.page.embargo
Collections
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/