LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB.

Wang J, An H, Mayo MW, Baldwin AS, Yarbrough WG
Cancer Cell. 2007 12 (3): 239-51

PMID: 17785205 · DOI:10.1016/j.ccr.2007.07.002

LZAP has been reported to inhibit cellular proliferation and clonogenic growth. Here, we report that decreased LZAP expression promoted cellular transformation, xenograft tumor growth, and xenograft tumor vascularity. Loss of LZAP also increased cellular invasion, and MMP-9 expression dependent on NF-kappaB. LZAP directly bound to RelA, impaired serine 536 phosphorylation of RelA, increased HDAC association with RelA, inhibited basal and stimulated NF-kappaB transcriptional activity, and was found at the promoter of selective NF-kappaB-responsive genes. LZAP protein levels were markedly decreased in 32% of primary HNSCCs (n = 28) and decreased LZAP levels in primary HNSCC correlated with increased expression of the NF-kappaB-regulated genes IL-8 and IkappaBalpha. In aggregate, these data support a role of LZAP in NF-kappaB regulation and tumor suppression.

MeSH Terms (22)

Animals Apoptosis Carcinoma, Squamous Cell Cell Transformation, Neoplastic Gene Expression Regulation Head and Neck Neoplasms HeLa Cells Histone Deacetylases Humans I-kappa B Proteins Interleukin-8 Intracellular Signaling Peptides and Proteins Matrix Metalloproteinase 9 Mice Mice, Nude Neoplasm Invasiveness Nerve Tissue Proteins NF-kappa B Transcription Factor RelA Transplantation, Heterologous Tumor Necrosis Factor-alpha Tumor Suppressor Proteins

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