P413 OXIDIZED-HEMOGLOBIN INDUCES INNATE IMMUNE CELL CHEMOTAXIS, MONOCYTE ARREST AND THEIR SUBINTIMAL MIGRATION INTO EARLY ATHEROSCLEROTIC TISSUE

Urological cancers are a very common type of cancer worldwide and have alarming high incidence and mortality rates, especially in kidney cancers, illustrate the urgent need for new therapeutic targets. Recent publications point to a deregulated COP9 signalosome (CSN)–cullin-RING ubiquitin-ligase (CRL) pathway which is here considered and investigated as potential target in urological cancers with strong focus on renal cell carcinomas (RCC). The CSN forms supercomplexes with CRLs in order to preserve protein homeostasis and was found deregulated in several cancer types. Examination of selected CSN–CRL pathway components in RCC patient samples and four RCC cell lines revealed an interesting deregulated p27Kip1-Skp2-CAND1 axis and two p27Kip1 point mutations in 786-O cells; p27Kip1V109G and p27Kip1I119T. The p27Kip1 mutants were detected in patients with RCC and appear to be responsible for an accelerated growth rate in 786-O cells. The occurrence of p27Kip1V109G and p27Kip1I119T in RCC makes the CSN–CRL pathway an attractive therapeutic target.