Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2001, PMID: 11060311

KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -induced block of p65/p50 nuclear translocation.

Yan, C; Wang, H; Boyd, D D

The 92-kDa type IV collagenase (MMP-9) plays a critical role in tissue remodeling. We undertook a study to determine whether the KiSS-1 gene, previously shown to suppress cancer spread (metastases), negatively regulates MMP-9 expression. Six cell lines positive for MMP-9 mRNA were deficient in KiSS-1 mRNA. One of these cell lines, HT-1080, stably transfected with a KiSS-1 expression construct, demonstrated substantially lower MMP-9 enzyme activity/protein and in vitro invasiveness. The lower MMP-9 enzyme activity reflected reduced steady-state mRNA levels which, in turn, was due to attenuated transcription. Activation of ERKs and JNKs by phorbol 12-myristate 13-acetate and tumor necrosis factor alpha, respectively, leading to increased MMP-9 amounts was not antagonized by KiSS-1 expression, suggesting that MAPK pathways modulating MMP-9 synthesis are not the target of KiSS-1. Although MMP-9 expression is regulated by AP-1, Sp1, and Ets transcription factors, KiSS-1 did not alter the binding of these factors to the MMP-9 promoter. However, NF-kappaB binding to the MMP-9 promoter required for expression of this collagenase was reduced by KiSS-1 expression. Diminished NF-kappaB binding reflected less p50/p65 in the nucleus secondary to increased IkappaBalpha levels in the cytosols of the KiSS-1 transfectants. Thus, KiSS-1 diminishes MMP-9 expression by effecting reduced NF-kappaB binding to the promoter.

Diseases/Pathways annotated by Medline MESH: Neoplasm Invasiveness
Document information provided by NCBI PubMed

Text Mining Data

92-kDa type IV collagenase ⊣ KiSS-1: " KiSS-1 represses 92-kDa type IV collagenase expression by down regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -induced block of p65/p50 nuclear translocation "

NF-kappa B ⊣ p65/p50: " KiSS-1 represses 92-kDa type IV collagenase expression by down regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha -induced block of p65/p50 nuclear translocation "

MMP-9 → Sp1: " Although MMP-9 expression is regulated by AP-1, Sp1 , and Ets transcription factors, KiSS-1 did not alter the binding of these factors to the MMP-9 promoter "

MMP-9 → AP-1: " Although MMP-9 expression is regulated by AP-1 , Sp1, and Ets transcription factors, KiSS-1 did not alter the binding of these factors to the MMP-9 promoter "

MMP-9 ⊣ KiSS-1: " However, NF-kappaB binding to the MMP-9 promoter required for expression of this collagenase was reduced by KiSS-1 expression "

NF-kappaB ⊣ KiSS-1: " However, NF-kappaB binding to the MMP-9 promoter required for expression of this collagenase was reduced by KiSS-1 expression "

MMP-9 ⊣ KiSS-1: " Thus, KiSS-1 diminishes MMP-9 expression by effecting reduced NF-kappaB binding to the promoter "

Manually curated Databases

No curated data.