SSX2 promotes the formation of a novel type of intranuclear lamin bodies

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Abstract

SSX proteins are normally restricted to spermatogenic cells, but ectopic expression can be observed in many types of human cancer. We recently demonstrated that SSX family members may contribute to tumorigenesis by modifying chromatin structure and, in specific settings, compromise chromatin stability. Here, we used normal and tumorigenic breast epithelial cell line models to further study the effect of ectopic expression of SSX2 on nuclear organization. We show that SSX2 induces the formation of a novel type of nucleoplasmic lamin bodies. Ectopic expression of SSX2 in various breast epithelial cell lines led to the formation of a previously undescribed type of intranuclear bodies containing both A and B type lamins but no other components of the nuclear lamina. SSX2-expressing cells contained a highly variable number of lamin bodies distributed throughout the nuclear space. SSX2-mediated establishment of intranuclear lamin bodies could not be linked to previous molecular interactions of SSX proteins, including polycomb proteins and the Mediator complex, but was, however, dependent on S-phase progression. These results reveal a novel interaction between SSX2 and lamins in the nucleoplasmic space. They further suggest that SSX2 promotes the formation of chromatin neighborhoods supporting the organization of lamins into nuclear bodies. We speculate that this may have implications for the organization and functional regulation of chromatin in cancer cells. Our study contributes to the further understanding of the biology of SSX proteins in tumorigenesis.

OriginalsprogEngelsk
Artikelnummer106121
TidsskriftThe International Journal of Biochemistry & Cell Biology
Vol/bind142
Antal sider8
ISSN1357-2725
DOI
StatusUdgivet - jan. 2022

Bibliografisk note

Funding Information:
This work was supported by Novo Nordisk Foundation (grant number NNF18SA0032928 ), Pink Tribute, Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat, the Danish Cancer Society (grant number R146-A9213-16-S2 ), the Academy of Geriatric Cancer Research (AgeCare), the Novo Nordisk Foundation (grant number NNF18OC0052303 ) and the Danish Research Council for Independent Research (grant number 6108-00372A ).

Publisher Copyright:
© 2021 Elsevier Ltd

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