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 p27(Kip1)-Skp2-CAND1 axis and two p27(Kip1) point mutations in 786-O cells; p27(Kip1)V109G and p27(Kip1)I119T. The p27(Kip1) mutants were detected in patients with RCC and appear to be responsible for an accelerated growth rate in 786-O cells. The occurrence of p27(Kip1)V109G and p27(Kip1)I119T in RCC makes the CSN-CRL pathway an attractive therapeutic target.
International review of cell and molecular biology. 2016 Feb 16 [Epub]
Linda Gummlich, Thilo Kähne, Michael Naumann, Ergin Kilic, Klaus Jung, Wolfgang Dubiel
Department of General, Visceral, Vascular and Thoracic Surgery, Division of Molecular Biology, Charité-Universitätsmedizin, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany., Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany., Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany., Department of Pathology, Charité-Universitätsmedizin, Berlin, Germany., Berlin Institute for Urological Research, Berlin, Germany; Department of Urology, Charité-Universitätsmedizin, Berlin, Germany., Department of General, Visceral, Vascular and Thoracic Surgery, Division of Molecular Biology, Charité-Universitätsmedizin, Berlin, Germany. Electronic address: .