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.