Clinical and Translational Oncology

, Volume 12, Issue 3, pp 160–165 | Cite as

Von Hippel-Lindau syndrome: molecular mechanisms of the disease

  • María J. CalzadaEmail author
Educational Series Molecular and Cellular Biology of Cancer


Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible for the development of renal carcinomas, pheochromocytomas and tumours in other organs. The gene product (pVHL) is a central component in the oxygen-sensing pathway through its role in the regulation of the hypoxia-inducible factor (HIF). Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes. However, although the role of pVHL in the regulation of HIF has proved to be important for tumour growth, other pVHL functions independent of HIF have been reported and help to explain why loss of VHL leads to renal cancer. Studies aimed to characterise other molecular pathways that shed light on its physiological roles as a gatekeeper gene in kidney and other organs will be very helpful for the development of novel anticancer therapies.


Von Hippel-Lindau HIFα Prolyl hydroxylase Renal cell carcinomas 


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© Feseo 2010

Authors and Affiliations

  1. 1.Hospital Universitario de la PrincesaUniversidad Autónoma de MadridMadridSpain

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