Networks of tumor suppressors

Sponsored by the Juan March Foundation, and organized by J Massague and M Serranno. Madrid, Spain, May 8–10, 2000.![][1] The concept of tumor suppressor networks comes as a logical consequence of the increasing understanding of the biology of tumor suppressor genes and oncogenes. Indeed, it has been gratifying to realize during the past decade that the products of tumor suppressor genes and oncogenes are often involved in the kind of guardian–delinquent relationship, or cat‐and‐mouse game suggested by the genetic evidence. Thus, some oncogenes directly cancel the protective activities of tumor suppressors and, reciprocally, there are some tumor suppressors that detect the presence of oncogenes and counteract their effects. Our understanding of the signaling network built by these gene products is still sketchy but rapidly growing (Figure 1), and this was the focus of the workshop ‘Tumor Suppressor Networks’.Figure 1. A roadmap to the tumor suppressor network. A scheme of the different pathways discussed at the workshop and their interconnectivities.### Oncogenes that inactivate tumor suppressorsThe Ras oncogene plays a central role in the transmission of external mitogenic signals to the cell. For this, Ras uses a number of effector pathways that can counteract the activity of certain tumor suppressors. Discussions on this topic at the Workshop are summarized under the following two subheadings.The Ras–Raf pathway . The activation of the Raf–Mek–Erk cascade of kinases by Ras is the main event responsible for the transmission of proliferative signals from the cell membrane to the nucleus. However, the transcriptional consequences of activating this cascade are still poorly defined. J. Downward (London, UK) reported preliminary data on the short term transcriptional effects of inducing Raf in a mammary epithelial cell line. Data from microarrayed chips revealed a substantial number of autocrine mitogens, survival factors and angiogenic factors that are upregulated upon Raf activation. Among these autocrine factors is … [1]: /embed/graphic-1.gif