VHL inactivation: A new road to senescence

Loss of the VHL tumor suppressor gene promotes cancer in several ways, including activation of the HIF transcription factors. HIF overexpression is associated with increased malignancy in many tumor types. So why is the spectrum of tumors associated with VHL loss restricted only to a few specific organs? In a recent paper in the March issue of Nature Cell Biology, Kaelin and colleagues provide a possible explanation, suggesting that VHL loss can also trigger senescence, a potent tumor suppressor mechanism.