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Superoxide dismutase-3 downmodulates laminin α5 expression in endothelial cells via Nuclear Factor kappa B signaling inhibition

ABSTRACT: The balance between laminins containing the α5 (LAMA5) or the α4 (LAMA4) subunits is determinant for the diapedesis of different leukocyte subtypes in inflammatory conditions. We have shown that the extracellular superoxide dismutase (SOD3) is a positive regulator of LAMA4, and this was associated with enhanced intratumor T cell infiltration in experimental and primary human cancers. Here we show that SOD3 overexpression in neoplastic or endothelial cells (ECs) downmodulates LAMA5 levels in implanted tumors. The inhibitory effect of SOD3 on LAMA5 expression occurs at the transcriptional level and is specific for SOD3, since LAMA5 levels are not changed by in SOD1-overexpressing cells. Global transcriptomic analyses revealed that SOD3 overexpression changes the transcription of 1,682 genes in ECs exposed to tumor secreted factors, being the canonical and non-canonical Nuclear Factor kappa B (NF-κB) pathways major SOD3 targets. Indeed, SOD3 reduced the transcription of well-known NF-κB target genes as well as the NF-κB-driven promoter activity in endothelial cells stimulated with tumor necrosis factor (TNF)-α, an inducer of NF-κB signaling

ORGANISM(S): Mus musculus

PROVIDER: GSE189247 | GEO | 2022/03/02

REPOSITORIES: GEO

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Extracellular Superoxide Dismutase Regulates the Expression of GTPase Guanine Nucleotide Exchange Factors (GEFs), GTPase-activating proteins (GAPs), and Rho Guanine nucleotide disassociation inhibitors (GDI)

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