LZAP, a putative tumor suppressor, selectively inhibits NF-κB

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-kappa B. LZAP directly bound to ReIA, impaired serine 536 phosphorylation of ReIA, increased HDAC association with RelA, inhibited basal and stimulated NF-kappa B transcriptional activity, and was found at the promoter of selective NF-kappa B-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-kappa B-regulated genes IL-8 and I kappa B alpha. In aggregate, these data support a role of LZAP in NF-kappa B regulation and tumor suppression.