Nuclear localisation of Aurora-A: its regulation and significance for Aurora-A functions in cancer.

The Aurora-A kinase regulates cell division, by controlling centrosome biology and spindle assembly. Cancer cells often display elevated levels of the kinase, due to amplification of the gene locus, increased transcription or post-translational modifications. Several inhibitors of Aurora-A activity have been developed as anti-cancer agents and are under evaluation in clinical trials. Although the well-known mitotic roles of Aurora-A point at chromosomal instability, a hallmark of cancer, as a major link between Aurora-A overexpression and disease, recent evidence highlights the existence of non-mitotic functions of potential relevance. Here we focus on a nuclear-localised fraction of Aurora-A with oncogenic roles. Interestingly, this pool would identify not only non-mitotic, but also kinase-independent functions of the kinase. We review existing data in the literature and databases, examining potential links between Aurora-A stabilisation and localisation, and discuss them in the perspective of a more effective targeting of Aurora-A in cancer therapy

Synthesis and biological investigation of 1,2,4-triazolo[4,3-a]azines as potential HSF1 inductors

Derivatives of fused 1,2,4-triazines containing heterocyclic and metallocene fragments were obtained by one-pot oxidative cyclization of heterocyclic hydrazones in the presence of hypervalent iodine(III) reagents. For 1,2,4-triazolo[4,3-a]azines, the ability to activate HSF1 was investigated. The obtained compounds were shown to increase the degree of HSF1 activation. It was shown that the 1,2,4-triazines can be used to induce Hsp70 expression and decrease the extent of mutant HTT aggregate formation

Epigenetics in renal cell cancer: mechanisms and clinical applications

Renal cell carcinoma (RCC) is characterized by an infrequent number of somatic mutations. By contrast, epigenetic aberrations are commonly found in RCC, indicating that epigenetic reprogramming is an important event in RCC development. Epigenetic alterations comprise several different aberrations, such as changes in histone modifications, DNA methylation, and microRNA levels, and occur in the most important signalling pathways in RCC, such as the von Hippel-Lindau disease tumour suppressor (VHL)-hypoxia-inducible factor (HIF) pathway, the WNT-beta-catenin pathway, and pathways involved in epithelial-mesenchymal transition. Owing to their involvement in these pathways and frequent occurrence in RCC, epigenetic alterations are regarded as potential biomarkers for the early detection of disease and for prediction of prognosis and treatment response. In addition, most of these alterations are potentially reversible, so they also provide new targets for therapy. At the moment, epigenetic biomarkers for RCC are not being used in clinical practice, but targeted epigenetic therapies are under investigation. Understanding the extent of epigenetic changes occurring in RCC and the mechanisms by which they influence disease progression and treatment response, as well as knowledge of current research on biomarkers and treatments, is crucial to successful clinical translation of epigenetics in RCC