SPANX Control of Lamin A/C Modulates Nuclear Architecture and Promotes Melanoma Growth.
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
30
03
2020
revised:
19
05
2020
accepted:
15
06
2020
pubmed:
24
6
2020
medline:
1
9
2021
entrez:
24
6
2020
Statut:
ppublish
Résumé
Mechanisms regulating nuclear organization control fundamental cellular processes, including the cell and chromatin organization. Their disorganization, including aberrant nuclear architecture, has been often implicated in cellular transformation. Here, we identify Lamin A, among proteins essential for nuclear architecture, as SPANX (sperm protein associated with the nucleus on the X chromosome), a cancer testis antigen previously linked to invasive tumor phenotypes, interacting protein in melanoma. SPANX interaction with Lamin A was mapped to the immunoglobulin fold-like domain, a region critical for Lamin A function, which is often mutated in laminopathies. SPANX downregulation in melanoma cell lines perturbed nuclear organization, decreased cell viability, and promoted senescence-associated phenotypes. Moreover, SPANX knockdown (KD) in melanoma cells promoted proliferation arrest, a phenotype mediated in part by IRF3/IL1A signaling. SPANX KD in melanoma cells also prompted the secretion of IL1A, which attenuated the proliferation of naïve melanoma cells. Identification of SPANX as a nuclear architecture complex component provides an unexpected insight into the regulation of Lamin A and its importance in melanoma. IMPLICATIONS: SPANX, a testis protein, interacts with LMNA and controls nuclear architecture and melanoma growth.
Identifiants
pubmed: 32571981
pii: 1541-7786.MCR-20-0291
doi: 10.1158/1541-7786.MCR-20-0291
pmc: PMC7541784
mid: NIHMS1605968
doi:
Substances chimiques
Lamin Type A
0
Lamins
0
Nuclear Proteins
0
lamin C protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1560-1573Subventions
Organisme : NCI NIH HHS
ID : R35 CA197465
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA114046
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224070
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202021
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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